A step-wise approach for establishing a multidisciplinary team for the management of tuberous sclerosis complex: a Delphi consensus report.

BACKGROUND: Tuberous sclerosis complex (TSC) is a rare autosomal dominant genetic disorder associated with mutations in TSC1 and TSC2 genes, upregulation of mammalian target of rapamycin signaling, and subsequent tumor formation in various organs. Due to the many manifestations of TSC and their potential complications, management requires the expertise of multiple medical disciplines. A multidisciplinary care approach is recommended by consensus guidelines. Use of multidisciplinary teams (MDTs) has been shown to be beneficial in treating other complex diseases, such as cancer. In a lifelong disease such as TSC, an MDT may facilitate the transition from pediatric to adult care. However, little guidance exists in the literature regarding how to organize an MDT in TSC. METHODS: To discuss the best approach to assembling an MDT, this project was initiated in October 2017 with a meeting of 12 physicians from various specialties and various countries. Following this first meeting, the experts generated statements on the most important aspects to implement in establishing an MDT for TSC by 3 rounds of selection using a Delphi process via electronic correspondence. Finally, TSC patient advocates reviewed the findings and provided additional insights from a patient perspective. RESULTS: A 3-step roadmap was recommended, starting with identifying a single individual to begin organizing care (Step 1), then establishing a small core team (Step 2), and finally, establishing a larger multi-disciplinary team (Step 3). Because of the multisystemic nature of TSC, the MDT should include specialists such as a neurologist, a neurosurgeon, a nephrologist, a urologist, a pulmonologist, an ophthalmologist, a cardiologist, a dermatologist, a geneticist, and a psychiatrist/psychologist. The MDT should recommend a care plan for each patient based on the individual's needs and in consultation with him/her or his/her family. Some of the most important aspects of an MDT that were agreed upon included identifying a case manager to help coordinate care, providing access to health care professionals of varying specialties, and including a lead physician who takes medical responsibility for patients' overall care. CONCLUSIONS: The results of our consensus provide guidance to support the initiation of an MDT in TSC

Distributions of bacteriohopanepolyols in lakes and coastal lagoons of the Azores Archipelago

Bacteriohopanepolyols (BHPs) are a diverse class of lipids produced by bacteria across a wide range of environments. In this study, we aim to further identify BHPs related to ecological niches and/or specific bacteria by characterizing the distribution of BHPs in suspended particulate matter (SPM) of the water column and in sediments in a range of lakes and coastal lagoons from the Azores Archipelago, as well as in a co-culture enriched for methanotrophs. Sediment samples from Azorean lakes with low-oxygen conditions during the summer months (i.e., Azul, Verde, Funda, and Negra) contain relatively high abundances of BHPs that are typically associated with methane-oxidizing (methanotrophic) bacteria (i.e., aminotetrol, aminopentol, and methylcarbamate-aminopentol), as well as the ethenolamine-BHPs (i.e., ethenolamine-BHpentol and ethenolamine-BHhexol) and the N-formylated aminoBHPs. Both ethenolamine-BHPs and N-formylated aminoBHPs were also detected in a methanotroph–methylotroph co-culture that was enriched from a lake. In the SPM of all water columns, bacteriohopanetetrol (BHT), BHT cyclitol ether, and aminotriol are the dominant BHPs. In SPM from Lake Funda, nucleoside BHPs (i.e., Me-adenosylhopaneHG-diMe (where HG refers to head group), N1-methylinosylhopane, 2Me-N1-inosylhopane, and Me-N1-inosylhopane) are present in low abundance or absent under oxic conditions but increase in concentration near the chemocline, suggesting potential in situ production of these nucleoside BHPs rather than an allochthonous origin. In contrast, sediments from shallow, well-mixed lakes (i.e., Empadadas, São Jorge, and Lomba) contain higher abundances of adenosylhopane and N1-methylinosylhopane, which likely originate from bacteria living in nearby soils. Based on our current results we revised the existing Rsoil index, which was previously used to infer terrestrial inputs to aquatic environments, to exclude any potential nucleosides produced in the lake water column (Rsoil-lake). In the coastal lagoons, Cubres East and Cubres West, methoxylated BHTs were detected, and higher abundances of ethenolamine-BHT were observed. This study highlights the diversity of BHPs in lakes and coastal lagoons and their potential as taxonomic markers for bacteria associated with certain ecological niches, which can be preserved in sedimentary records

Validation of miR-1228-3p as Housekeeping for MicroRNA Analysis in Liquid Biopsies from Colorectal Cancer Patients

BACKGROUND: Circulating microRNA (miRNA) analysis is a growing research field. However, it usually requires an endogenous control or housekeeping (HK) in order to normalize expression of specific miRNAs throughout different samples. Unfortunately, no adequate HK for circulating miRNA analysis is still known in the colorectal cancer (CRC) context whereas several have been suggested. Hence, our aims were to validate the previously suggested miR-1228-3p as HK for CRC studies, to compare its suitability with the widely used miR-16-5p, and to evaluate the influence of hemolysis on both miRNAs. METHODS: We analyzed by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) the expression of miR-1228-3p, miR-16-5p and the spike-in cel-miR-39 in a set of 297 plasmas (92 CRC, 101 advanced adenomas -AA-, and 100 controls) and 213 serum samples (59 CRC, 74 AA and 80 controls). We also analyzed both miRNAs depending on the hemolysis degree in 7 plasmas and 31 serums. RESULTS: Levels of miR-1228-3p and miR-16-5p did not show significant differences between groups although miR-16-5p exhibited more variability in plasma and serum samples. Importantly, the combination of cel-miR-39 and miR-1228-3p was the most stable one. Moreover, we observed that miR-16-5p was significantly influenced by hemolysis in contrast with miR-1228-3p that exhibited no correlation with this confounding factor in both biofluids. CONCLUSION: MiR-1228-3p has been validated as an adequate endogenous control for circulating miRNA analysis in CRC and AA liquid biopsies

Explanation for the increase in high altitude water on Mars observed by NOMAD during the 2018 global dust storm

The Nadir and Occultation for MArs Discovery (NOMAD) instrument on board ExoMars Trace Gas Orbiter (TGO) measured a large increase in water vapor at altitudes in the range of 40‐100 km during the 2018 global dust storm on Mars. Using a three‐dimensional general circulation model, we examine the mechanism responsible for the enhancement of water vapor in the upper atmosphere. Experiments with different prescribed vertical profiles of dust show that when more dust is present higher in the atmosphere the temperature increases and the amount of water ascending over the tropics is not limited by saturation until reaching heights of 70‐100 km. The warmer temperatures allow more water to ascend to the mesosphere. Photochemical simulations show a strong increase in high‐altitude atomic hydrogen following the high‐altitude water vapor increase by a few days

Plasma MicroRNA Signature Validation for Early Detection of Colorectal Cancer

OBJECTIVES: Specific microRNA (miRNA) signatures in biological fluids can facilitate earlier detection of the tumors being then minimally invasive diagnostic biomarkers. Circulating miRNAs have also emerged as promising diagnostic biomarkers for colorectal cancer (CRC) screening. In this study, we investigated the performance of a specific signature of miRNA in plasma samples to design a robust predictive model that can distinguish healthy individuals from those with CRC or advanced adenomas (AA) diseases. METHODS: Case control study of 297 patients from 8 Spanish centers including 100 healthy individuals, 101 diagnosed with AA, and 96 CRC cases. Quantitative real-time reverse transcription was used to quantify a signature of miRNA (miRNA19a, miRNA19b, miRNA15b, miRNA29a, miRNA335, and miRNA18a) in plasma samples. Binary classifiers (Support Vector Machine [SVM] linear, SVM radial, and SVM polynomial) were built for the best predictive model. RESULTS: Area under receiving operating characteristic curve of 0.92 (95% confidence interval 0.871-0.962) was obtained retrieving a model with a sensitivity of 0.85 and specificity of 0.90, positive predictive value of 0.94, and negative predictive value of 0.76 when advanced neoplasms (CRC and AA) were compared with healthy individuals. CONCLUSIONS: We identified and validated a signature of 6 miRNAs (miRNA19a, miRNA19b, miRNA15b, miRNA29a, miRNA335, and miRNA18a) as predictors that can differentiate significantly patients with CRC and AA from those who are healthy. However, large-scale validation studies in asymptomatic screening participants should be conducted

The Atmospheric Chemistry Suite (ACS) of Three Spectrometers for the ExoMars 2016 Trace Gas Orbiter

The Atmospheric Chemistry Suite (ACS) package is an element of the Russian contribution to the ESA-Roscosmos ExoMars 2016 Trace Gas Orbiter (TGO) mission. ACS consists of three separate infrared spectrometers, sharing common mechanical, electrical, and thermal interfaces. This ensemble of spectrometers has been designed and developed in response to the Trace Gas Orbiter mission objectives that specifically address the requirement of high sensitivity instruments to enable the unambiguous detection of trace gases of potential geophysical or biological interest. For this reason, ACS embarks a set of instruments achieving simultaneously very high accuracy (ppt level), very high resolving power (>10,000) and large spectral coverage (0.7 to 17 μm—the visible to thermal infrared range). The near-infrared (NIR) channel is a versatile spectrometer covering the 0.7–1.6 μm spectral range with a resolving power of ∼20,000. NIR employs the combination of an echelle grating with an AOTF (Acousto-Optical Tunable Filter) as diffraction order selector. This channel will be mainly operated in solar occultation and nadir, and can also perform limb observations. The scientific goals of NIR are the measurements of water vapor, aerosols, and dayside or night side airglows. The mid-infrared (MIR) channel is a cross-dispersion echelle instrument dedicated to solar occultation measurements in the 2.2–4.4 μm range. MIR achieves a resolving power of >50,000. It has been designed to accomplish the most sensitive measurements ever of the trace gases present in the Martian atmosphere. The thermal-infrared channel (TIRVIM) is a 2-inch double pendulum Fourier-transform spectrometer encompassing the spectral range of 1.7–17 μm with apodized resolution varying from 0.2 to 1.3 cm−1. TIRVIM is primarily dedicated to profiling temperature from the surface up to ∼60 km and to monitor aerosol abundance in nadir. TIRVIM also has a limb and solar occultation capability. The technical concept of the instrument, its accommodation on the spacecraft, the optical designs as well as some of the calibrations, and the expected performances for its three channels are described

Carbon dioxide retrievals from NOMAD‐SO on ESA’s ExoMars Trace Gas Orbiter and temperature profiles retrievals with the hydrostatic equilibrium equation: 2. Temperature variabilities in the mesosphere at Mars terminator.

The Solar Occultation (SO) channel of the Nadir and Occultation for Mars Discovery (NOMAD) instrument scans the Martian atmosphere since 21 April 2018. In this work, we present a subset of the NOMAD SO data measured at the mesosphere. We focused on a spectral range that started to be recorded in Martian year (MY) 35. A total of 968 vertical profiles of carbon dioxide density and temperature covering MY 35 and the beginning of MY 36 were investigated until 135° of solar longitude. We compared 47 profiles with co-located profiles of the Mars Climate Sounder onboard the Mars Reconnaissance Orbiter. Most profiles show a good agreement as SO temperatures are only 1.8 K higher, but some biases lead to an average absolute difference of 7.4°K. The SO data set is also compared with simulations from the Global Environmental Multiscale-Mars general circulation model. Both data sets are in good agreement except for the presence of a cold layer in the winter hemisphere and a warm layer at dawn in the Northern hemisphere for solar longitudes between 240° and 360°. Five profiles contain temperatures lower than the limit for CO2 condensation. Strong warm layers were found in 13.5% of the profiles. They are present mainly at dawn and in the winter hemisphere, while the Northern dusks appear featureless. The data set mainly covers high latitudes around 60° and we derived some non-migrating tides. In the Southern winter hemisphere, we derived apparent zonal wavenumber-1 (WN-1) and WN-3 tidal components with a maximum amplitude of 10% and 5% at 63 km, respectively

Water Vapor Vertical Profiles on Mars in Dust Storms Observed by TGO/NOMAD

It has been suggested that dust storms efficiently transport water vapor from the near‐surface to the middle atmosphere on Mars. Knowledge of the water vapor vertical profile during dust storms is important to understand water escape. During Martian Year 34, two dust storms occurred on Mars: a global dust storm (June to mid‐September 2018) and a regional storm (January 2019). Here we present water vapor vertical profiles in the periods of the two dust storms (Ls = 162–260° and Ls = 298–345°) from the solar occultation measurements by Nadir and Occultation for Mars Discovery (NOMAD) onboard ExoMars Trace Gas Orbiter (TGO). We show a significant increase of water vapor abundance in the middle atmosphere (40–100 km) during the global dust storm. The water enhancement rapidly occurs following the onset of the storm (Ls~190°) and has a peak at the most active period (Ls~200°). Water vapor reaches very high altitudes (up to 100 km) with a volume mixing ratio of ~50 ppm. The water vapor abundance in the middle atmosphere shows high values consistently at 60°S‐60°N at the growth phase of the dust storm (Ls = 195°–220°), and peaks at latitudes greater than 60°S at the decay phase (Ls = 220°–260°). This is explained by the seasonal change of meridional circulation: from equinoctial Hadley circulation (two cells) to the solstitial one (a single pole‐to‐pole cell). We also find a conspicuous increase of water vapor density in the middle atmosphere at the period of the regional dust storm (Ls = 322–327°), in particular at latitudes greater than 60°S

Accuracy of genomic prediction of dry matter intake in Dutch Holsteins using sequence variants from meta-analyses

We evaluated the accuracy of biology informed genomic prediction for dry matter intake in 2,162 Dutch Holstein cows. Sequence variants were selected from meta-analyses including GWAS summary statistics for QTL and metabolomic QTL in several dairy and crossbred beef populations. Selected variants were prioritized in GBLUP models in a five-fold cross-validation. The accuracies were compared to genomic prediction based on routine 50k genotype data. The average accuracy for the 50k scenario was 0.683. Adding selected sequence variants in the GBLUP model did not improve the accuracies for dry matter intake. Next steps will include testing Bayesian variable selection methods to prioritize variants in genomic prediction for dry matter intake