Background & Aim
To assess consonant proficiency and velopharyngeal function in 10‐year‐old children born with unilateral cleft lip and palate (UCLP) within the Scandcleft project.
Methods & ...Procedures
Three parallel group, randomized, clinical trials were undertaken as an international multicentre study by nine cleft teams in five countries. Three different surgical protocols for primary palate repair (Arm B–Lip and soft palate closure at 3–4 months, hard palate closure at 36 months, Arm C–Lip closure at 3–4 months, hard and soft palate closure at 12 months, and Arm D–Lip closure at 3–4 months combined with a single‐layer closure of the hard palate using a vomer flap, soft palate closure at 12 months) were tested against a common procedure (Arm A–Lip and soft palate closure at 3–4 months followed by hard palate closure at 12 months) in the total cohort of 431 children born with a non‐syndromic UCLP. Speech audio and video recordings of 399 children were available and perceptually analysed. Percentage of consonants correct (PCC) from a naming test, an overall rating of velopharyngeal competence (VPC) (VPC‐Rate), and a composite measure (VPC‐Sum) were reported.
Outcomes & Results
The mean levels of consonant proficiency (PCC score) in the trial arms were 86–92% and between 58% and 83% of the children had VPC (VPC‐Sum). Only 50–73% of the participants had a consonant proficiency level with their peers. Girls performed better throughout. Long delay of the hard palate repair (Arm B) indicated lower PCC and simultaneous hard and soft palate closure higher (Arm C). However, the proportion of participants with primary VPC (not including velopharyngeal surgeries) was highest in Arm B (68%) and lowest in Arm C (47%).
Conclusions & Implications
The speech outcome in terms of PCC and VPC was low across the trials. The different protocols had their pros and cons and there is no obvious evidence to recommend any of the protocols as superior. Aspects other than primary surgical method, such as time after velopharyngeal surgery, surgical experience, hearing level, language difficulties and speech therapy, need to be thoroughly reviewed for a better understanding of what has affected speech outcome at 10 years.
WHAT THIS PAPER ADDS
What is already known on the subject
Speech outcomes at 10 years of age in children treated for UCLP are sparse and contradictory. Previous studies have examined speech outcomes and the relationship with surgical intervention in 5‐year‐olds.
What this study adds to the existing knowledge
Speech outcomes based on standardized assessment in a large group of 10‐year‐old children born with UCLP and surgically treated according to different protocols are presented. While speech therapy had been provided, a large proportion of the children across treatment protocols still needed further speech therapy.
What are the potential or actual clinical implications of this work?
Aspects other than surgery and speech function might add to the understanding of what affects speech outcome. Effective speech therapy should be available for children in addition to primary surgical repair of the cleft and secondary surgeries if needed.
KELT-9 b, the hottest known exoplanet, with
T
eq
~ 4400 K, is the archetype of a new planet class known as ultra-hot Jupiters. These exoplanets are presumed to have an atmosphere dominated by neutral ...and ionized atomic species. In particular, H
α
and H
β
Balmer lines have been detected in the KELT-9 b upper atmosphere, suggesting that hydrogen is filling the planetary Roche lobe and escaping from the planet. In this work, we detected
δ
Scuti-type stellar pulsation (with a period
P
puls
= 7.54 ± 0.12 h) and studied the Rossiter-McLaughlin effect (finding a spin-orbit angle
λ
= −85.01° ± 0.23°) prior to focussing on the Balmer lines (H
α
to H
ζ
) in the optical transmission spectrum of KELT-9 b. Our HARPS-N data show significant absorption for H
α
to H
δ
. The precise line shapes of the H
α
, H
β
, and H
γ
absorptions allow us to put constraints on the thermospheric temperature. Moreover, the mass loss rate, and the excited hydrogen population of KELT-9 b are also constrained, thanks to a retrieval analysis performed with a new atmospheric model. We retrieved a thermospheric temperature of
T
= 13 200
−720
+800
K and a mass loss rate of
Ṁ
= 10
12.8±0.3
g s
−1
when the atmosphere was assumed to be in hydrodynamical expansion and in local thermodynamic equilibrium (LTE). Since the thermospheres of hot Jupiters are not expected to be in LTE, we explored atmospheric structures with non-Boltzmann equilibrium for the population of the excited hydrogen. We do not find strong statistical evidence in favor of a departure from LTE. However, our non-LTE scenario suggests that a departure from the Boltzmann equilibrium may not be sufficient to explain the retrieved low number densities of the excited hydrogen. In non-LTE, Saha equilibrium departure via photo-ionization, is also likely to be necessary to explain the data.
Since the start of the Wide-angle Search for Planets (WASP) program, more than 160 transiting exoplanets have been discovered in the WASP data. In the past, possible transit-like events identified by ...the WASP pipeline have been vetted by human inspection to eliminate false alarms and obvious false positives. The goal of this paper is to assess the effectiveness of machine learning as a fast, automated, and reliable means of performing the same functions on ground-based wide-field transit-survey data without human intervention. To this end, we have created training and test data sets made up of stellar light curves showing a variety of signal types including planetary transits, eclipsing binaries, variable stars, and non-periodic signals. We use a combination of machine-learning methods including Random Forest Classifiers (RFCs) and convolutional neural networks (CNNs) to distinguish between the different types of signals. The final algorithms correctly identify planets in the test data ∼90 per cent of the time, although each method on its own has a significant fraction of false positives. We find that in practice, a combination of different methods offers the best approach to identifying the most promising exoplanet transit candidates in data from WASP, and by extension similar transit surveys.
ER-positive (ER+ ) breast cancer includes all of the intrinsic molecular subtypes, although the luminal A and B subtypes predominate. In this study, we evaluated the ability of six clinically ...relevant genomic signatures to predict relapse in patients with ER+ tumors treated with adjuvant tamoxifen only.
Four microarray datasets were combined and research-based versions of PAM50 intrinsic subtyping and risk of relapse (PAM50-ROR) score, 21-gene recurrence score (OncotypeDX), Mammaprint, Rotterdam 76 gene, index of sensitivity to endocrine therapy (SET) and an estrogen-induced gene set were evaluated. Distant relapse-free survival (DRFS) was estimated by Kaplan–Meier and log-rank tests, and multivariable analyses were done using Cox regression analysis. Harrell's C-index was also used to estimate performance.
All signatures were prognostic in patients with ER+ node-negative tumors, whereas most were prognostic in ER+ node-positive disease. Among the signatures evaluated, PAM50-ROR, OncotypeDX, Mammaprint and SET were consistently found to be independent predictors of relapse. A combination of all signatures significantly increased the performance prediction. Importantly, low-risk tumors (>90% DRFS at 8.5 years) were identified by the majority of signatures only within node-negative disease, and these tumors were mostly luminal A (78%–100%).
Most established genomic signatures were successful in outcome predictions in ER+ breast cancer and provided statistically independent information. From a clinical perspective, multiple signatures combined together most accurately predicted outcome, but a common finding was that each signature identified a subset of luminal A patients with node-negative disease who might be considered suitable candidates for adjuvant endocrine therapy alone.
ABSTRACT
We report the discovery and characterization of WASP-180Ab, a hot Jupiter confirmed by the detection of its Doppler shadow and by measuring its mass using radial velocities. We find the 0.9 ... ± 0.1 MJup, 1.24 ± 0.04 RJup planet to be in a misaligned, retrograde orbit around an F7 star with Teff = 6500 K and a moderate rotation speed of vsin i⋆ = 19.9 km s−1. The host star is the primary of a V = 10.7 binary, where a secondary separated by ∼5 arcsec (∼1200 au) contributes ∼ 30 per cent of the light. WASP-180Ab therefore adds to a small sample of transiting hot Jupiters known in binary systems. A 4.6-d modulation seen in the WASP data is likely to be the rotational modulation of the companion star, WASP-180B.
Evidence is strengthening for the morphological evaluation of tumor infiltrating lymphocytes (TILs) in breast cancer. Herein, the concepts for TILs assessment are laid out by pathologists to ...facilitate their wider evaluation and consistent interpretation. The goal of this article is to promote the evaluation of TILs as a biomarker in research, clinical trial settings and day-to-day practice.
The morphological evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer (BC) is gaining momentum as evidence strengthens for the clinical relevance of this immunological biomarker. Accumulating evidence suggests that the extent of lymphocytic infiltration in tumor tissue can be assessed as a major parameter by evaluation of hematoxylin and eosin (H&E)-stained tumor sections. TILs have been shown to provide prognostic and potentially predictive value, particularly in triple-negative and human epidermal growth factor receptor 2-overexpressing BC.
A standardized methodology for evaluating TILs is now needed as a prerequisite for integrating this parameter in standard histopathological practice, in a research setting as well as in clinical trials. This article reviews current data on the clinical validity and utility of TILs in BC in an effort to foster better knowledge and insight in this rapidly evolving field, and to develop a standardized methodology for visual assessment on H&E sections, acknowledging the future potential of molecular/multiplexed approaches.
The methodology provided is sufficiently detailed to offer a uniformly applied, pragmatic starting point and improve consistency and reproducibility in the measurement of TILs for future studies.
This paper describes a method for determination of 27 mycotoxins and other secondary metabolites in maize silage. The method focuses on analytes which are known to be produced by common maize and ...maize-silage contaminants. A simple pH-buffered sample extraction was developed on the basis of a very fast and simple method for analysis of multiple pesticide residues in food known as QuEChERS. The buffering effectively ensured a stable pH in samples of both well-ensiled maize (pH < 4) and of hot spots with fungal infection (pH > 7). No further clean-up was performed before analysis using liquid chromatography-tandem mass spectrometry. The method was successfully validated for determination of eight analytes qualitatively and 19 quantitatively. Matrix-matched calibration standards were used giving recoveries ranging from 37% to 201% with the majority between 60% and 115%. Repeatability (5-27% RSDr) and intra-laboratory reproducibility (7-35% RSDIR) was determined. The limit of detection (LOD) for the quantitatively validated analytes ranged from 1 to 739 µg kg⁻¹. Validation results for citrinin, fumonisin B₁ and fumonisin B₂ were unsatisfying. The method was applied to 20 selected silage samples and alternariol monomethyl ether, andrastin A, alternariol, citreoisocoumarin, deoxynivalenol, enniatin B, fumigaclavine A, gliotoxin, marcfortine A and B, mycophenolic acid, nivalenol, roquefortine A and C and zearalenone were detected. graphic removed
Liraglutide is a glucagon-like peptide-1 (GLP-1) analog developed for type 2 diabetes. Long-term liraglutide exposure in rodents was associated with thyroid C-cell hyperplasia and tumors. Here, we ...report data supporting a GLP-1 receptor-mediated mechanism for these changes in rodents. The GLP-1 receptor was localized to rodent C-cells. GLP-1 receptor agonists stimulated calcitonin release, up-regulation of calcitonin gene expression, and subsequently C-cell hyperplasia in rats and, to a lesser extent, in mice. In contrast, humans and/or cynomolgus monkeys had low GLP-1 receptor expression in thyroid C-cells, and GLP-1 receptor agonists did not activate adenylate cyclase or generate calcitonin release in primates. Moreover, 20 months of liraglutide treatment (at >60 times human exposure levels) did not lead to C-cell hyperplasia in monkeys. Mean calcitonin levels in patients exposed to liraglutide for 2 yr remained at the lower end of the normal range, and there was no difference in the proportion of patients with calcitonin levels increasing above the clinically relevant cutoff level of 20 pg/ml. Our findings delineate important species-specific differences in GLP-1 receptor expression and action in the thyroid. Nevertheless, the long-term consequences of sustained GLP-1 receptor activation in the human thyroid remain unknown and merit further investigation.
The species-specific activation of the thyroid GLP-1 receptor is described in rodent C-cells that diverges markedly from the biology of GLP-1 receptor action in the monkey and human thyroid gland.
Radar Soundings of the Ionosphere of Mars Gurnett, D. A; Kirchner, D. L; Huff, R. L ...
Science (American Association for the Advancement of Science),
12/2005, Letnik:
310, Številka:
5756
Journal Article
Recenzirano
Odprti dostop
We report the first radar soundings of the ionosphere of Mars with the MARSIS (Mars Advanced Radar for Subsurface and Ionosphere Sounding) instrument on board the orbiting Mars Express spacecraft. ...Several types of ionospheric echoes are observed, ranging from vertical echoes caused by specular reflection from the horizontally stratified ionosphere to a wide variety of oblique and diffuse echoes. The oblique echoes are believed to arise mainly from ionospheric structures associated with the complex crustal magnetic fields of Mars. Echoes at the electron plasma frequency and the cyclotron period also provide measurements of the local electron density and magnetic field strength.
The height of mountain ranges reflects the balance between tectonic rock uplift, crustal strength and surface denudation. Tectonic deformation and surface denudation are interdependent, however, and ...feedback mechanisms—in particular, the potential link to climate—are subjects of intense debate. Spatial variations in fluvial denudation rate caused by precipitation gradients are known to provide first-order controls on mountain range width, crustal deformation rates and rock uplift. Moreover, limits to crustal strength are thought to constrain the maximum elevation of large continental plateaus, such as those in Tibet and the central Andes. There are indications that the general height of mountain ranges is also directly influenced by the extent of glaciation through an efficient denudation mechanism known as the glacial buzzsaw. Here we use a global analysis of topography and show that variations in maximum mountain height correlate closely with climate-controlled gradients in snowline altitude for many high mountain ranges across orogenic ages and tectonic styles. With the aid of a numerical model, we further demonstrate how a combination of erosional destruction of topography above the snowline by glacier-sliding and commensurate isostatic landscape uplift caused by erosional unloading can explain observations of maximum mountain height by driving elevations towards an altitude window just below the snowline. The model thereby self-consistently produces the hypsometric signature of the glacial buzzsaw, and suggests that differences in the height of mountain ranges mainly reflect variations in local climate rather than tectonic forces.
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