Follicular and endocrine dose responses according to anti-Müllerian hormone levels in IVF patients treated with a novel human recombinant FSH (FE 999049)

Objective: To study the association between serum anti-Mullerian hormone (AMH) levels and follicular development and endocrine responses induced by increasing doses (5.2-12.1 mu g/day) of a novel recombinant human FSH (rhFSH, FE 999049) in patients undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) in a GnRH antagonist protocol. Design: Secondary analysis of a randomized controlled trial with stratified randomization according to AMH (lower stratum: 5.0-14.9 pmol/l; higher stratum: 15.0-44.9 pmol/l). Patients: Infertile women of good prognosis (n = 265). Measurements: Follicular development and endocrine parameters during controlled ovarian stimulation (COS) with rhFSH. Results: Serum FSH levels increased with increasing rhFSH doses and steady-state levels for each dose were similar in both AMH strata. In the whole study population, significant (P = 12 mm, and serum levels of oestradiol, inhibin B, inhibin A and progesterone at end of stimulation. In comparison with the higher AMH stratum, patients in the lower AMH stratum had significantly different slopes of the dose-response curves for these hormones, and no clear dose-related increase was observed for the number of follicles in these patients. Conclusions: Dose-response relationships between rhFSH and follicular development and endocrine parameters are significantly different for IVF/ICSI patients with lower and higher serum AMH levels at start of COS

Assessment of metabolomic and proteomic biomarkers in detection and prognosis of progression of renal function in chronic kidney disease

Chronic kidney disease (CKD) is part of a number of systemic and renal diseases and may reach epidemic proportions over the next decade. Efforts have been made to improve diagnosis and management of CKD. We hypothesised that combining metabolomic and proteomic approaches could generate a more systemic and complete view of the disease mechanisms. To test this approach, we examined samples from a cohort of 49 patients representing different stages of CKD. Urine samples were analysed for proteomic changes using capillary electrophoresis-mass spectrometry and urine and plasma samples for metabolomic changes using different mass spectrometry-based techniques. The training set included 20 CKD patients selected according to their estimated glomerular filtration rate (eGFR) at mild (59.9±16.5 mL/min/1.73 m2; n = 10) or advanced (8.9±4.5 mL/min/1.73 m2; n = 10) CKD and the remaining 29 patients left for the test set. We identified a panel of 76 statistically significant metabolites and peptides that correlated with CKD in the training set. We combined these biomarkers in different classifiers and then performed correlation analyses with eGFR at baseline and follow-up after 2.8±0.8 years in the test set. A solely plasma metabolite biomarker-based classifier significantly correlated with the loss of kidney function in the test set at baseline and follow-up (ρ = −0.8031; p<0.0001 and ρ = −0.6009; p = 0.0019, respectively). Similarly, a urinary metabolite biomarker-based classifier did reveal significant association to kidney function (ρ = −0.6557; p = 0.0001 and ρ = −0.6574; p = 0.0005). A classifier utilising 46 identified urinary peptide biomarkers performed statistically equivalent to the urinary and plasma metabolite classifier (ρ = −0.7752; p<0.0001 and ρ = −0.8400; p<0.0001). The combination of both urinary proteomic and urinary and plasma metabolic biomarkers did not improve the correlation with eGFR. In conclusion, we found excellent association of plasma and urinary metabolites and urinary peptides with kidney function, and disease progression, but no added value in combining the different biomarkers data

Evaluation of three lidar scanning strategies for turbulence measurements

Several errors occur when a traditional Doppler beam swinging (DBS) or velocity–azimuth display (VAD) strategy is used to measure turbulence with a lidar. To mitigate some of these errors, a scanning strategy was recently developed which employs six beam positions to independently estimate the <i>u</i>, <i>v</i>, and <i>w</i> velocity variances and covariances. In order to assess the ability of these different scanning techniques to measure turbulence, a Halo scanning lidar, WindCube v2 pulsed lidar, and ZephIR continuous wave lidar were deployed at field sites in Oklahoma and Colorado with collocated sonic anemometers.</br></br>Results indicate that the six-beam strategy mitigates some of the errors caused by VAD and DBS scans, but the strategy is strongly affected by errors in the variance measured at the different beam positions. The ZephIR and WindCube lidars overestimated horizontal variance values by over 60 % under unstable conditions as a result of variance contamination, where additional variance components contaminate the true value of the variance. A correction method was developed for the WindCube lidar that uses variance calculated from the vertical beam position to reduce variance contamination in the <i>u</i> and <i>v</i> variance components. The correction method reduced WindCube variance estimates by over 20 % at both the Oklahoma and Colorado sites under unstable conditions, when variance contamination is largest. This correction method can be easily applied to other lidars that contain a vertical beam position and is a promising method for accurately estimating turbulence with commercially available lidars

Remote-sensing and radiosonde datasets collected in the San Luis Valley during the LAPSE-RATE campaign

In July 2018, the International Society for Atmospheric Research using Remotely piloted Aircraft (ISARRA) hosted a flight week to showcase the role remotely piloted aircraft systems (RPASs) can have in filling the atmospheric data gap. This campaign was called Lower Atmospheric Process Studies at Elevation &ndash; a Remotely-piloted Aircraft Team Experiment (LAPSE-RATE). In support of this campaign, ground-based remote and in situ systems were also deployed for the campaign. The University of Oklahoma deployed the Collaborative Lower Atmospheric Mobile Profiling System (CLAMPS), the University of Colorado deployed two Doppler wind lidars, and the National Severe Storms Laboratory deployed a mobile mesonet with the ability to launch radiosondes. This paper focuses on the data products from these instruments that result in profiles of the atmospheric state. The data are publicly available in the Zenodo LAPSE-RATE community portal (https://zenodo.org/communities/lapse-rate/, 19 January 2021). The profile data discussed are available at https://doi.org/10.5281/zenodo.3780623 (Bell and Klein,&nbsp;2020), https://doi.org/10.5281/zenodo.3780593 (Bell et&nbsp;al.,&nbsp;2020b), https://doi.org/10.5281/zenodo.3727224 (Bell et&nbsp;al.,&nbsp;2020a), https://doi.org/10.5281/zenodo.3738175 (Waugh,&nbsp;2020b), https://doi.org/10.5281/zenodo.3720444 (Waugh,&nbsp;2020a), and https://doi.org/10.5281/zenodo.3698228 (Lundquist et&nbsp;al.,&nbsp;2020). &nbsp;</p

Turbulence dissipation rate estimated from lidar observations during the LAPSE-RATE field campaign

The International Society for Atmospheric Research using Remotely-piloted Aircraft (ISARRA) hosted a flight week in July 2018 to demonstrate unmanned aircraft systems' (UASs) capabilities in sampling the atmospheric boundary layer. This week-long experiment was called the Lower Atmospheric Profiling Studies at Elevation &ndash; a Remotely-piloted Aircraft Team Experiment (LAPSE-RATE) field campaign. Numerous remotely piloted aircraft and ground-based instruments were deployed with the objective of capturing meso- and microscale phenomena in the atmospheric boundary layer. The University of Oklahoma deployed one Halo Streamline lidar, and the University of Colorado Boulder deployed two WindCube lidars. In this paper, we use data collected from these Doppler lidars to estimate turbulence dissipation rate throughout the campaign. We observe large temporal variability of turbulence dissipation close to the surface with the WindCube lidars that is not detected by the Halo Streamline. However, the Halo lidar enables estimating dissipation rate within the whole boundary layer, where a diurnal variability emerges. We also find a higher correspondence in turbulence dissipation between the WindCube lidars, which are not co-located, compared to the Halo and WindCube lidar that are co-located, suggesting a significant influence of measurement volume on the retrieved values of dissipation rate. This dataset has been submitted to Zenodo (Sanchez Gomez and Lundquist, 2020) for free and is openly accessible (https://doi.org/10.5281/zenodo.4399967). &nbsp;</p

Individualized versus conventional ovarian stimulation for in vitro fertilization:a multicenter, randomized, controlled, assessor-blinded, phase 3 noninferiority trial

Objective: To compare the efficacy and safety of follitropin delta, a new human recombinant FSH with individualized dosing based on serum antimüllerian hormone (AMH) and body weight, with conventional follitropin alfa dosing for ovarian stimulation in women undergoing IVF. Design: Randomized, multicenter, assessor-blinded, noninferiority trial (ESTHER-1). Setting: Reproductive medicine clinics. Patient(s): A total of 1,329 women (aged 18–40 years). Intervention(s): Follitropin delta (AMH &lt;15 pmol/L: 12 μg/d; AMH ≥15 pmol/L: 0.10–0.19 μg/kg/d; maximum 12 μg/d), or follitropin alfa (150 IU/d for 5 days, potential subsequent dose adjustments; maximum 450 IU/d). Main Outcomes Measure(s): Ongoing pregnancy and ongoing implantation rates; noninferiority margins −8.0%. Result(s): Ongoing pregnancy (30.7% vs. 31.6%; difference −0.9% [95% confidence interval (CI) −5.9% to 4.1%]), ongoing implantation (35.2% vs. 35.8%; −0.6% [95% CI −6.1% to 4.8%]), and live birth (29.8% vs. 30.7%; −0.9% [95% CI −5.8% to 4.0%]) rates were similar for individualized follitropin delta and conventional follitropin alfa. Individualized follitropin delta resulted in more women with target response (8–14 oocytes) (43.3% vs. 38.4%), fewer poor responses (fewer than four oocytes in patients with AMH &lt;15 pmol/L) (11.8% vs. 17.9%), fewer excessive responses (≥15 or ≥20 oocytes in patients with AMH ≥15 pmol/L) (27.9% vs. 35.1% and 10.1% vs. 15.6%, respectively), and fewer measures taken to prevent ovarian hyperstimulation syndrome (2.3% vs. 4.5%), despite similar oocyte yield (10.0 ± 5.6 vs. 10.4 ± 6.5) and similar blastocyst numbers (3.3 ± 2.8 vs. 3.5 ± 3.2), and less gonadotropin use (90.0 ± 25.3 vs. 103.7 ± 33.6 μg). Conclusion(s): Optimizing ovarian response in IVF by individualized dosing according to pretreatment patient characteristics results in similar efficacy and improved safety compared with conventional ovarian stimulation

Entanglement in the quantum Ising model

We study the asymptotic scaling of the entanglement of a block of spins for the ground state of the one-dimensional quantum Ising model with transverse field. When the field is sufficiently strong, the entanglement grows at most logarithmically in the number of spins. The proof utilises a transformation to a model of classical probability called the continuum random-cluster model, and is based on a property of the latter model termed ratio weak-mixing. Our proof applies equally to a large class of disordered interactions

The mysteries of mammatus clouds: Observations and formation mechanisms

Mammatus clouds are an intriguing enigma of atmospheric fluid dynamics and cloud physics. Most commonly observed on the underside of cumulonimbus anvils, mammatus also occur on the underside of cirrus, cirrocumulus, altocumulus, altostratus, and stratocumulus, as well as in contrails from jet aircraft and pyrocumulus ash clouds from volcanic eruptions. Despite their aesthetic appearance, mammatus have been the subject of few quantitative research studies. Observations of mammatus have been obtained largely through serendipitous opportunities with a single observing system (e.g., aircraft penetrations, visual observations, lidar, radar) or tangential observations from field programs with other objectives. Theories describing mammatus remain untested, as adequate measurements for validation do not exist because of the small distance scales and short time scales of mammatus. Modeling studies of mammatus are virtually nonexistent. As a result, relatively little is known about the environment, formation mechanisms, properties, microphysics, and dynamics of mammatus. This paper presents a review of mammatus clouds that addresses these mysteries. Previous observations of mammatus and proposed formation mechanisms are discussed. These hypothesized mechanisms are anvil subsidence, subcloud evaporation/sublimation, melting, hydrometeor fallout, cloud-base detrainment instability, radiative effects, gravity waves, Kelvin-Helmholtz instability, Rayleigh-Taylor instability, and Rayleigh-Bénard-like convection. Other issues addressed in this paper include whether mammatus are composed of ice or liquid water hydrometeors, why mammatus are smooth, what controls the temporal and spatial scales and organization of individual mammatus lobes, and what are the properties of volcanic ash clouds that produce mammatus? The similarities and differences between mammatus, virga, stalactites, and reticular clouds are also discussed. Finally, because much still remains to be learned, research opportunities are described for using mammatus as a window into the microphysical, turbulent, and dynamical processes occurring on the underside of clouds. © 2006 American Meteorological Society

Comparable low-level mosaicism in affected and non affected tissue of a complex CDH patient

In this paper we present the detailed clinical and cytogenetic analysis of a prenatally detected complex Congenital Diaphragmatic Hernia (CDH) patient with a mosaic unbalanced translocation (5;12). High-resolution whole genome SNP array confirmed a low-level mosaicism (20%) in uncultured cells, underlining the value of array technology for identification studies. Subsequently, targeted Fluorescence In-Situ Hybridization in postmortem collected tissues demonstrated a similar low-level mosaicism, independently of the affected status of the tissue. Thus, a higher incidence of the genetic aberration in affected organs as lung and diaphragm cannot explain the severe phenotype of this complex CDH patient. Comparison with other described chromosome 5p and 12p anomalies indicated that half of the features presented in our patient (including the diaphragm defect) could be attributed to both chromosomal areas. In contrast, a few features such as the palpebral downslant, the broad nasal bridge, the micrognathia, microcephaly, abnormal dermatoglyphics and IUGR better fitted the 5p associated syndromes only. This study underlines the fact that low-level mosaicism can be associated with severe birth defects including CDH. The contribution of mosaicism to human diseases and specifically to congenital anomalies and spontaneous abortions becomes more and more accepted, although its phenotypic consequences are poorly described phenomena leading to counseling issues. Therefore, thorough follow-up of mosaic aberrations such as presented here is indicated in order to provide genetic counselors a more evidence based prediction of fetal prognosis in the future

Common carotid intima media thickness and ankle-brachial pressure index correlate with local but not global atheroma burden:a cross sectional study using whole body magnetic resonance angiography

Common carotid intima media thickness (CIMT) and ankle brachial pressure index (ABPI) are used as surrogate marker of atherosclerosis, and have been shown to correlate with arterial stiffness, however their correlation with global atherosclerotic burden has not been previously assessed. We compare CIMT and ABPI with atheroma burden as measured by whole body magnetic resonance angiography (WB-MRA).50 patients with symptomatic peripheral arterial disease were recruited. CIMT was measured using ultrasound while rest and exercise ABPI were performed. WB-MRA was performed in a 1.5T MRI scanner using 4 volume acquisitions with a divided dose of intravenous gadolinium gadoterate meglumine (Dotarem, Guerbet, FR). The WB-MRA data was divided into 31 anatomical arterial segments with each scored according to degree of luminal narrowing: 0 = normal, 1 = <50%, 2 = 50-70%, 3 = 70-99%, 4 = vessel occlusion. The segment scores were summed and from this a standardized atheroma score was calculated.The atherosclerotic burden was high with a standardised atheroma score of 39.5±11. Common CIMT showed a positive correlation with the whole body atheroma score (β 0.32, p = 0.045), however this was due to its strong correlation with the neck and thoracic segments (β 0.42 p = 0.01) with no correlation with the rest of the body. ABPI correlated with the whole body atheroma score (β -0.39, p = 0.012), which was due to a strong correlation with the ilio-femoral vessels with no correlation with the thoracic or neck vessels. On multiple linear regression, no correlation between CIMT and global atheroma burden was present (β 0.13 p = 0.45), while the correlation between ABPI and atheroma burden persisted (β -0.45 p = 0.005).ABPI but not CIMT correlates with global atheroma burden as measured by whole body contrast enhanced magnetic resonance angiography in a population with symptomatic peripheral arterial disease. However this is primarily due to a strong correlation with ilio-femoral atheroma burden