A reflective, metal-rich atmosphere for GJ 1214b from its JWST phase curve.

There are no planets intermediate in size between Earth and Neptune in our Solar System, yet these objects are found around a substantial fraction of other stars1. Population statistics show that close-in planets in this size range bifurcate into two classes on the basis of their radii2,3. It is proposed that the group with larger radii (referred to as 'sub-Neptunes') is distinguished by having hydrogen-dominated atmospheres that are a few percent of the total mass of the planets4. GJ 1214b is an archetype sub-Neptune that has been observed extensively using transmission spectroscopy to test this hypothesis5-14. However, the measured spectra are featureless, and thus inconclusive, due to the presence of high-altitude aerosols in the planet's atmosphere. Here we report a spectroscopic thermal phase curve of GJ 1214b obtained with the James Webb Space Telescope (JWST) in the mid-infrared. The dayside and nightside spectra (average brightness temperatures of 553 ± 9 and 437 ± 19 K, respectively) each show more than 3σ evidence of absorption features, with H2O as the most likely cause in both. The measured global thermal emission implies that GJ 1214b's Bond albedo is 0.51 ± 0.06. Comparison between the spectroscopic phase curve data and three-dimensional models of GJ 1214b reveal a planet with a high metallicity atmosphere blanketed by a thick and highly reflective layer of clouds or haze.

Real-World Testing Practices, Treatment Patterns and Clinical Outcomes in Patients from Central Eastern Europe with EGFR-Mutated Advanced Non-Small Cell Lung Cancer: A Retrospective Chart Review Study (REFLECT).

The targeted therapy with tyrosine kinase inhibitors (TKIs) against the epidermal growth factor receptor mutation (EGFRm) in advanced non-small cell lung cancer (NSCLC) changed the treatment paradigm. REFLECT study (NCT04031898) explored EGFR/T790M testing and treatment patterns in EGFRm NSCLC patients receiving first- or second-generation (1G/2G) EGFR TKIs as front-line (1L) in eight countries. Pooled data from Central Eastern Europe (CEE) countries from this study (Bulgaria, Poland, Romania, Slovenia) are presented here. This physician-led chart review study was conducted in patients with confirmed-EGFRm NSCLC initiating 1L 1G/2G EGFR TKIs between 2015-2018. The CEE cohort included 389 patients receiving 1L erlotinib (37%), afatinib (34%), and gefitinib (29%). Overall, 320 (82%) patients discontinued 1L, and 298 (77%) progression events were registered. Median progression free survival on 1L TKIs was 14.0 (95% CI: 12.6-15.6) months. Median overall survival from 1L start was 26.6 (95% CI: 24.1-29.0) months. Attrition rate between 1L and next line was 30%. Among patients with 1L progression, 200 (67%) were tested for T790M and 58% were positive. This first CEE analysis of treatments and outcomes in EGFRm NSCLC patients highlights the importance of using the most efficacious therapies currently available in 1L to reduce attrition and improve patient outcomes.

Effectiveness of BNT162b2 and mRNA-1273 Second Doses and Boosters for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection and SARS-CoV-2-Related Hospitalizations: A Statewide Report From the Minnesota Electronic Health Record Consortium.

Using vaccine data combined with electronic health records, we report that mRNA boosters provide greater protection than a 2-dose regimen against SARS-CoV-2 infection and related hospitalizations. The benefit of a booster was more evident in the elderly and those with comorbidities.

Automated Decision Support for Drug-Induced Long QT.

Advancements in clinical informatics and translational genomics are changing the way we practice medicine. Automated decision support currently helps providers adjust prescribing patterns to reduce the likelihood of QT prolongation based upon drug-drug interaction. A similar approach is being explored for drug-gene interaction. Like many adverse drug reactions, QT prolongation can be influenced by variability in genetic factors. However, drug-induced QT prolongation can occur in the absence of any known ion channel gene abnormalities. We therefore review differences between congenital long QT syndrome and drug-induced long QT syndrome, and we underscore the need for decision support that integrates EKG data.

Implementation of wide-scale pharmacogenetic testing in primary care.

The convergence of translational genomics and biomedical informatics has changed healthcare delivery. Institutional consortia have begun implementing lab testing and decision support for drug-gene interactions. Aggregate datasets are now revealing the impact of clinical decision support for drug-gene interactions. Given the pleiotropic nature of pharmacogenes, interdisciplinary teams and robust clinical decision support tools must exist within an informatics framework built to be flexible and capable of cross-talk between clinical specialties. Navigation of the challenges presented with the implementation of five steps to build a genetics program infrastructure requires the expertise of multiple healthcare professionals. Ultimately, this manuscript describes our efforts to place pharmacogenomics in the hands of the primary care provider integrating this information into a patient's healthcare over their lifetime.

Chronic Kidney Disease in Agricultural Communities.

Patients residing in agricultural communities have a high risk of developing chronic kidney disease. In the Great Plains, geo-environmental risk factors (eg, variable climate, temperature, air quality, water quality, and drought) combine with agro-environmental risk factors (eg, exposure to fertilizers, soil conditioners, herbicides, fungicides, and pesticides) to increase risk for toxic nephropathy. However, research defining the specific influence of agricultural chemicals on the progression of kidney disease in rural communities has been somewhat limited. By linking retrospective clinical data within electronic medical records to environmental data from sources like US Environmental Protection Agency, analytical models are beginning to provide insight into the impact of agricultural practices on the rate of progression for kidney disease in rural communities.

CYP2C19 genotype, physician prescribing pattern, and risk for long QT on serotonin selective reuptake inhibitors.

Aim: To examine the impact of CYP2C19 genotype on selective serotonin reuptake inhibitor (SSRI) prescribing patterns. Patients & methods: Observational cohort containing 507 unique individuals receiving an SSRI prescription with CYP2C19 genotype already in their electronic medical record. Genotype was distributed as follows: n = 360 (71%) had no loss of function alleles, 136 (26.8%) had one loss of function allele and 11 (2.2%) had two loss of function alleles. Results & conclusion: For poor metabolizers exposed to sertraline, citalopram or escitalopram, providers changed prescribing patterns in response to alerts in the electronic medical record by either changing the drug, changing the dose or monitoring serial EKGs longitudinally. For intermediate metabolizers exposed to sertraline, citalopram or escitalopram, no alert was needed (mean QTc = 440.338 ms [SD = 31.1273] for CYP2C19*1/*1, mean QTc = 440.371 ms [SD = 29.2706] for CYP2C19*1/*2; p = 0.995).

Learning from Longitudinal Data in Electronic Health Record and Genetic Data to Improve Cardiovascular Event Prediction.

Current approaches to predicting a cardiovascular disease (CVD) event rely on conventional risk factors and cross-sectional data. In this study, we applied machine learning and deep learning models to 10-year CVD event prediction by using longitudinal electronic health record (EHR) and genetic data. Our study cohort included 109, 490 individuals. In the first experiment, we extracted aggregated and longitudinal features from EHR. We applied logistic regression, random forests, gradient boosting trees, convolutional neural networks (CNN) and recurrent neural networks with long short-term memory (LSTM) units. In the second experiment, we applied a late-fusion approach to incorporate genetic features. We compared the performance with approaches currently utilized in routine clinical practice - American College of Cardiology and the American Heart Association (ACC/AHA) Pooled Cohort Risk Equation. Our results indicated that incorporating longitudinal feature lead to better event prediction. Combining genetic features through a late-fusion approach can further improve CVD prediction, underscoring the importance of integrating relevant genetic data whenever available.

An ultrahot gas-giant exoplanet with a stratosphere.

Infrared radiation emitted from a planet contains information about the chemical composition and vertical temperature profile of its atmosphere. If upper layers are cooler than lower layers, molecular gases will produce absorption features in the planetary thermal spectrum. Conversely, if there is a stratosphere-where temperature increases with altitude-these molecular features will be observed in emission. It has been suggested that stratospheres could form in highly irradiated exoplanets, but the extent to which this occurs is unresolved both theoretically and observationally. A previous claim for the presence of a stratosphere remains open to question, owing to the challenges posed by the highly variable host star and the low spectral resolution of the measurements. Here we report a near-infrared thermal spectrum for the ultrahot gas giant WASP-121b, which has an equilibrium temperature of approximately 2,500 kelvin. Water is resolved in emission, providing a detection of an exoplanet stratosphere at 5σ confidence. These observations imply that a substantial fraction of incident stellar radiation is retained at high altitudes in the atmosphere, possibly by absorbing chemical species such as gaseous vanadium oxide and titanium oxide.

Decreasing the critical value of hemoglobin required for physician notification reduces the rate of blood transfusions.

Red blood cell transfusions have been cited as one of the most overused therapeutic interventions in the USA. Excessively aggressive transfusion practices may be driven by mandatory physician notification of critical hemoglobin values that do not generally require transfusion. We examined the effect of decreasing the critical value of hemoglobin from 8 to 7 g/dL at our institution. Along with this change, mandatory provider notification for readings between 7 and 8 g/dL was rescinded. Transfusion rates were compared retrospectively during paired 5-month periods for patients presenting in three key hemoglobin ranges (6.00-6.99, 7.00-7.99, and 8.00-8.99 g/dL). A change in transfusion practices was hypothesized in the 7-8 g/dL range, which was no longer labeled critical and for which mandated physician calls were rescinded. Transfusion rates showed a statistically significant 8% decrease (P≤0.0001) during the 5-month period post change in our transfusion practices. This decrease in the 7.00-7.99 g/dL range was significantly greater than the 2% decrease observed in either the 6-6.99 g/dL (P=0.0017) or 8-8.99 g/dL (P≤0.0001) range. Cost savings of up to $700,000/year were extrapolated from our results showing 491 fewer units of red blood cells transfused during the 5-month post change. These cost savings do not take into account the additional impact of complications associated with blood transfusions.

Terrestrial aftermath of the Moon-forming impact.

Much of the Earth's mantle was melted in the Moon-forming impact. Gases that were not partially soluble in the melt, such as water and CO2, formed a thick, deep atmosphere surrounding the post-impact Earth. This atmosphere was opaque to thermal radiation, allowing heat to escape to space only at the runaway greenhouse threshold of approximately 100 W m(-2). The duration of this runaway greenhouse stage was limited to approximately 10 Myr by the internal energy and tidal heating, ending with a partially crystalline uppermost mantle and a solid deep mantle. At this point, the crust was able to cool efficiently and solidified at the surface. After the condensation of the water ocean, approximately 100 bar of CO2 remained in the atmosphere, creating a solar-heated greenhouse, while the surface cooled to approximately 500 K. Almost all this CO2 had to be sequestered by subduction into the mantle by 3.8 Ga, when the geological record indicates the presence of life and hence a habitable environment. The deep CO2 sequestration into the mantle could be explained by a rapid subduction of the old oceanic crust, such that the top of the crust would remain cold and retain its CO2. Kinematically, these episodes would be required to have both fast subduction (and hence seafloor spreading) and old crust. Hadean oceanic crust that formed from hot mantle would have been thicker than modern crust, and therefore only old crust underlain by cool mantle lithosphere could subduct. Once subduction started, the basaltic crust would turn into dense eclogite, increasing the rate of subduction. The rapid subduction would stop when the young partially frozen crust from the rapidly spreading ridge entered the subduction zone.

Outcome of nicotine replacement therapy in patients admitted to ICU: a randomized controlled double-blind prospective pilot study.

BACKGROUND: The effect of nicotine withdrawal in smokers admitted to the ICU is not well understood, so the role of nicotine replacement therapy (NRT) in those patients is controversial. OBJECTIVE: To determine whether NRT in ICU patients affects the need for sedatives/analgesics, ventilator days, and ICU stay. METHODS: In a 20-bed ICU, 40 subjects were randomized to either a 21 mg nicotine patch or a placebo nicotine patch daily until either ICU discharge, transfer to a medical floor, or 10 weeks in the ICU. We collected data on sedatives/analgesics use during ICU stay and use and duration of mechanical ventilation . RESULTS: There were 27 male and 13 female subjects. The mean age was 57.4 y in the intervention group and 52.5 y in the control group. The mean Acute Physiology and Chronic Health Evaluation II score was 14.3 in the intervention group and 13.8 in the control group. The mean ICU stay was 4.5 d in the intervention group and 7 d in the control group. The mean number of days on ventilator was 1.9 in the intervention group and 3.5 in the control group. The number of days on sedation/analgesia was less in the intervention group than in the control group. CONCLUSIONS: Although ICU stay and ventilator days decreased numerically in this pilot study, statistically there was no beneficial effect from NRT. (International Standard Randomised Controlled Trial Register ISRCTN66928309).