To assess the accuracy of principal investigators' (PIs) predictions about three events for their own clinical trials: positivity on trial primary outcomes, successful recruitment and timely trial ...completion.
A short, electronic survey was used to elicit subjective probabilities within seven months of trial registration. When trial results became available, prediction skill was calculated using Brier scores (BS) and compared against uninformative prediction (i.e. predicting 50% all of the time).
740 PIs returned surveys (16.7% response rate). Predictions on all three events tended to exceed observed event frequency. Averaged PI skill did not surpass uninformative predictions (e.g., BS = 0.25) for primary outcomes (BS = 0.25, 95% CI 0.20, 0.30) and were significantly worse for recruitment and timeline predictions (BS 0.38, 95% CI 0.33, 0.42; BS = 0.52, 95% CI 0.50, 0.55, respectively). PIs showed poor calibration for primary outcome, recruitment, and timelines (calibration index = 0.064, 0.150 and 0.406, respectively), modest discrimination in primary outcome predictions (AUC = 0.76, 95% CI 0.65, 0.85) but minimal discrimination in the other two outcomes (AUC = 0.64, 95% CI 0.57, 0.70; and 0.55, 95% CI 0.47, 0.62, respectively).
PIs showed overconfidence in favorable outcomes and exhibited limited skill in predicting scientific or operational outcomes for their own trials. They nevertheless showed modest ability to discriminate between positive and non-positive trial outcomes. Low survey response rates may limit generalizability.
We systematically searched for gravity- and Rossby-mode period spacing patterns in Kepler eclipsing binaries with \(\gamma\) Doradus pulsators. These stars provide an excellent opportunity to test ...the theory of tidal synchronisation and angular momentum transport in F- and A-type stars. We discovered 35 systems that show clear patterns, including the spectroscopic binary KIC 10080943. Combined with 45 non-eclipsing binaries with \(\gamma\) Dor components that have been found using pulsation timing, we measured their near-core rotation rates and asymptotic period spacings. We find that many stars are tidally locked if the orbital periods are shorter than 10 days, in which the near-core rotation periods given by the traditional approximation of rotation (TAR) are consistent with the orbital period. Compared to the single stars, \(\gamma\) Dor stars in binaries tend to have slower near-core rotation rates, likely a consequence of tidal spin-down. We also find three stars that have extremely slow near-core rotation rates. To explain these, we hypothesise that unstable tidally excited oscillations can transfer angular momentum from the star to the orbit, and slow the star below synchronism, a process we refer to as `inverse tides'.
ABSTRACT
We study the fraction of stars in and around the δ Scuti instability strip that are pulsating, using Gaia DR2 parallaxes to derive precise luminosities. We classify a sample of over 15 000 ...Kepler A and F stars into δ Sct and non-δ Sct stars, paying close attention to variability that could have other origins. We find that 18 per cent of the δ Sct stars have their dominant frequency above the Kepler long-cadence Nyquist frequency (periods < 1 h), and 30 per cent have some super-Nyquist variability. We analyse the pulsator fraction as a function of effective temperature and luminosity, finding that many stars in the δ Sct instability strip do not pulsate. The pulsator fraction peaks at just over 70 per cent in the middle of the instability strip. The results are insensitive to the amplitude threshold used to identify the pulsators. We define a new empirical instability strip based on the observed pulsator fraction that is systematically hotter than theoretical strips currently in use. The stellar temperatures, luminosities, and pulsation classifications are provided in an online catalogue.
Strong magnetic fields in chemically peculiar A-type (Ap) stars typically suppress low-overtone pressure modes (p modes) but allow high-overtone p modes to be driven. KIC 11296437 is the first star ...to show both. We obtained and analysed a Subaru spectrum, from which we show that KIC 11296437 has abundances similar to other magnetic Ap stars, and we estimate a mean magnetic field modulus of \(2.8\pm0.5\) kG. The same spectrum rules out a double-lined spectroscopic binary, and we use other techniques to rule out binarity over a wide parameter space, so the two pulsation types originate in one \(\delta\) Sct--roAp hybrid pulsator. We construct stellar models depleted in helium and demonstrate that helium settling is second to magnetic damping in suppressing low-overtone p modes in Ap stars. We compute the magnetic damping effect for selected p and g modes, and find that modes with frequencies similar to the fundamental mode are driven for polar field strengths \(\lesssim4\) kG, while other low-overtone p modes are driven for polar field strengths up to \(\sim\)1.5 kG. We find that the high-order g modes commonly observed in \(\gamma\) Dor stars are heavily damped by polar fields stronger than 1--4 kG, with the damping being stronger for higher radial orders. We therefore explain the observation that no magnetic Ap stars have been observed as \(\gamma\) Dor stars. We use our helium-depleted models to calculate the \(\delta\) Sct instability strip for metallic-lined A (Am) stars, and find that driving from a Rosseland mean opacity bump at $\sim$$5\times10^4\( K caused by the discontinuous H-ionization edge in bound-free opacity explains the observation of \)\delta$ Sct pulsations in Am stars.
Recent developments in atmospheric remote sensing from satellites have made it possible to resolve daily emission plumes from industrial point sources around the globe. Wind rotation aggregation ...coupled with statistical fitting is commonly used to extract emission estimates from these observations. These methods are used here to investigate how the Coriolis effect influences the trajectory of observed emission plumes as well as to assess the impact of this influence on satellite-derived emission estimates. Of the 16 industrial sites investigated, 9 showed the expected curvature for the hemisphere that they reside in, 5 showed no or negligible curvature, and 2 showed opposing or unusual curvature. The sites that showed conflicting curvature reside in topographically diverse regions, where strong meso-γ-scale (2–20 km) turbulence dominates over larger synoptic circulation patterns. For high-curvature cases, the assumption that the wind-rotated plume aggregate is symmetrically distributed across the downwind axis breaks down, which impairs the quality of statistical fitting procedures. Using annual NOx emissions from Matimba power station as a test case, not compensating for Coriolis curvature resulted in an underestimation of ∼ 9 % on average for the years 2018 to 2021. This study is the first formal observation of the Coriolis effect and its influence on satellite-derived emission estimates, and it highlights both the variability in the emission calculation methods and the need for a standardised scheme for these data to act as evidence for regulators.
ABSTRACT
We perform mode identification for five δ Scuti stars in the Pleiades star cluster, using custom light curves from K2 photometry. By creating échelle diagrams, we identify radial and dipole ...mode ridges, comprising a total of 28 radial and 16 dipole modes across the five stars. We also suggest possible identities for those modes that lie offset from the radial and dipole ridges. We calculate non-rotating stellar pulsation models to verify our mode identifications, finding good agreement within the age and metallicity constraints of the cluster. We also find that for all stars, the least dense models are preferred, reflecting the lower density of these oblate, rotating stars. Three of the five stars show rotationally split multiplets. We conclude that the sample shows promise for asteroseismic rotation rates, masses, and ages with rotating models in the future. Our preliminary modelling also indicates some sensitivity to the helium abundance.
Background
ProGlide is a percutaneous suture‐mediated closure device used in arterial and venous closure following percutaneous intervention. Risk of vascular complications from use, particularly ...related to failure in hemostasis, or acute vessel closure, remains significant and often related to improper suture deployment. We describe a technique of ultrasound‐guided ProGlide deployment in transfemoral transcatheter aortic valve implantation (TF‐TAVI).
Aims
The aim of this study is to assess vascular outcomes for ultrasound‐guided deployment of ProGlide vascular closure devices in patients undergoing TF‐TAVI.
Methods
We collected relevant clinical data of patients undergoing TAVI in a large volume centre. Primary outcome: main access Valve Academic Research Consortium 3 (VARC‐3) major vascular complication. Secondary outcome: any major/minor VARC‐3 vascular complication, its type (bleed or ischemia), and treatment required (medical, percutaneous, or surgical). We performed inverse weighting propensity score analysis to compare the population undergoing ultrasound‐guided versus conventional ProGlide deployment for main TAVI access. Ultrasound technique for ProGlide insertion was performed as described below.
Results
Five hundred and seventeen patients undergoing TF‐TAVI were included.
Primary outcome: In 126 (ultrasound‐guided) and 391 (conventional ProGlide insertion), 0% versus 1.8% (p < 0.001) had a major VARC‐3 vascular complication, respectively.
Secondary outcome: 0.8% (one minor VARC‐3 bleed) vs 4.1% (13 bleeds and three occlusions) had any VARC‐3 vascular complication (major and minor) (p < 0.001). Surgical treatment of vascular complication was required in 0.8% versus 1.3% (p = NS).
Conclusions
Ultrasound‐guided deployment of ProGlide for vascular closure reduced the risk of major vascular complications in a large population undergoing TAVI.
We recently reported that the tetra(ethylene glycol) derivative of benzothiazole aniline, BTA-EG4, acts as an amyloid-binding small molecule that promotes dendritic spine density and cognitive ...function in wild-type mice. This raised the possibility that BTA-EG4 may benefit the functional decline seen in Alzheimer's disease (AD). In the present study, we directly tested whether BTA-EG4 improves dendritic spine density and cognitive function in a well-established mouse model of AD carrying mutations in APP, PS1 and tau (APPswe;PS1M146V;tauP301L, 3xTg AD mice). We found that daily injections of BTA-EG4 for 2weeks improved dendritic spine density and cognitive function of 3xTg AD mice in an age-dependent manner. Specifically, BTA-EG4 promoted both dendritic spine density and morphology alterations in cortical layers II/III and in the hippocampus at 6–10months of age compared to vehicle-injected mice. However, at 13–16months of age, only cortical spine density was improved without changes in spine morphology. The changes in dendritic spine density correlated with Ras activity, such that 6–10month old BTA-EG4 injected 3xTg AD mice had increased Ras activity in the cortex and hippocampus, while 13–16month old mice only trended toward an increase in Ras activity in the cortex. Finally, BTA-EG4 injected 3xTg AD mice at 6–10months of age showed improved learning and memory; however, only minimal improvement was observed at 13–16months of age. This behavioral improvement corresponds to a decrease in soluble Aβ 40 levels. Taken together, these findings suggest that BTA-EG4 may be beneficial in ameliorating the synaptic loss seen in early AD.
•BTA-EG4 rescues synapse loss seen in a mouse model of Alzheimer disease.•BTA-EG4 promotes spinogenesis through Ras signaling in 3xTg AD mice.•BTA-EG4 improves learning and memory in 3xTg AD mice.•The effect of BTA-EG4 on spinogenesis and cognitive function was age-dependent.•Our findings suggest that BTA-EG4 may be useful in novel AD therapies.
There are currently no approved treatments for peanut allergy.
To assess the efficacy and adverse events of epicutaneous immunotherapy with a peanut patch among peanut-allergic children.
Phase 3, ...randomized, double-blind, placebo-controlled trial conducted at 31 sites in 5 countries between January 8, 2016, and August 18, 2017. Participants included peanut-allergic children (aged 4-11 years n = 356 without a history of a severe anaphylactic reaction) developing objective symptoms during a double-blind, placebo-controlled food challenge at an eliciting dose of 300 mg or less of peanut protein.
Daily treatment with peanut patch containing either 250 μg of peanut protein (n = 238) or placebo (n = 118) for 12 months.
The primary outcome was the percentage difference in responders between the peanut patch and placebo patch based on eliciting dose (highest dose at which objective signs/symptoms of an immediate hypersensitivity reaction developed) determined by food challenges at baseline and month 12. Participants with baseline eliciting dose of 10 mg or less were responders if the posttreatment eliciting dose was 300 mg or more; participants with baseline eliciting dose greater than 10 to 300 mg were responders if the posttreatment eliciting dose was 1000 mg or more. A threshold of 15% or more on the lower bound of a 95% CI around responder rate difference was prespecified to determine a positive trial result. Adverse event evaluation included collection of treatment-emergent adverse events (TEAEs).
Among 356 participants randomized (median age, 7 years; 61.2% male), 89.9% completed the trial; the mean treatment adherence was 98.5%. The responder rate was 35.3% with peanut-patch treatment vs 13.6% with placebo (difference, 21.7% 95% CI, 12.4%-29.8%; P < .001). The prespecified lower bound of the CI threshold was not met. TEAEs, primarily patch application site reactions, occurred in 95.4% and 89% of active and placebo groups, respectively. The all-causes rate of discontinuation was 10.5% in the peanut-patch group vs 9.3% in the placebo group.
Among peanut-allergic children aged 4 to 11 years, the percentage difference in responders at 12 months with the 250-μg peanut-patch therapy vs placebo was 21.7% and was statistically significant, but did not meet the prespecified lower bound of the confidence interval criterion for a positive trial result. The clinical relevance of not meeting this lower bound of the confidence interval with respect to the treatment of peanut-allergic children with epicutaneous immunotherapy remains to be determined.
ClinicalTrials.gov Identifier: NCT02636699.
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