25 research outputs found
Identification of the top TESS objects of interest for atmospheric characterization of transiting exoplanets with JWST
Funding: Funding for the TESS mission is provided by NASA's Science Mission Directorate. This work makes use of observations from the LCOGT network. Part of the LCOGT telescope time was granted by NOIRLab through the Mid-Scale Innovations Program (MSIP). MSIP is funded by NSF. This paper is based on observations made with the MuSCAT3 instrument, developed by the Astrobiology Center and under financial support by JSPS KAKENHI (grant No. JP18H05439) and JST PRESTO (grant No. JPMJPR1775), at Faulkes Telescope North on Maui, HI, operated by the Las Cumbres Observatory. This paper makes use of data from the MEarth Project, which is a collaboration between Harvard University and the Smithsonian Astrophysical Observatory. The MEarth Project acknowledges funding from the David and Lucile Packard Fellowship for Science and Engineering, the National Science Foundation under grant Nos. AST-0807690, AST-1109468, AST-1616624 and AST-1004488 (Alan T. Waterman Award), the National Aeronautics and Space Administration under grant No. 80NSSC18K0476 issued through the XRP Program, and the John Templeton Foundation. C.M. would like to gratefully acknowledge the entire Dragonfly Telephoto Array team, and Bob Abraham in particular, for allowing their telescope bright time to be put to use observing exoplanets. B.J.H. acknowledges support from the Future Investigators in NASA Earth and Space Science and Technology (FINESST) program (grant No. 80NSSC20K1551) and support by NASA under grant No. 80GSFC21M0002. K.A.C. and C.N.W. acknowledge support from the TESS mission via subaward s3449 from MIT. D.R.C. and C.A.C. acknowledge support from NASA through the XRP grant No. 18-2XRP18_2-0007. C.A.C. acknowledges that this research was carried out at the Jet Propulsion Laboratory, California Institute of Technology, under a contract with the National Aeronautics and Space Administration (80NM0018D0004). S.Z. and A.B. acknowledge support from the Israel Ministry of Science and Technology (grant No. 3-18143). The research leading to these results has received funding from the ARC grant for Concerted Research Actions, financed by the Wallonia-Brussels Federation. TRAPPIST is funded by the Belgian Fund for Scientific Research (Fond National de la Recherche Scientifique, FNRS) under the grant No. PDR T.0120.21. The postdoctoral fellowship of K.B. is funded by F.R.S.-FNRS grant No. T.0109.20 and by the Francqui Foundation. H.P.O.'s contribution has been carried out within the framework of the NCCR PlanetS supported by the Swiss National Science Foundation under grant Nos. 51NF40_182901 and 51NF40_205606. F.J.P. acknowledges financial support from the grant No. CEX2021-001131-S funded by MCIN/AEI/ 10.13039/501100011033. A.J. acknowledges support from ANID—Millennium Science Initiative—ICN12_009 and from FONDECYT project 1210718. Z.L.D. acknowledges the MIT Presidential Fellowship and that this material is based upon work supported by the National Science Foundation Graduate Research Fellowship under grant No. 1745302. P.R. acknowledges support from the National Science Foundation grant No. 1952545. This work is partly supported by JSPS KAKENHI grant Nos. JP17H04574, JP18H05439, JP21K20376; JST CREST grant No. JPMJCR1761; and Astrobiology Center SATELLITE Research project AB022006. This publication benefits from the support of the French Community of Belgium in the context of the FRIA Doctoral Grant awarded to M.T. D.D. acknowledges support from TESS Guest Investigator Program grant Nos. 80NSSC22K1353, 80NSSC22K0185, and 80NSSC23K0769. A.B. acknowledges the support of M.V. Lomonosov Moscow State University Program of Development. T.D. was supported in part by the McDonnell Center for the Space Sciences. V.K. acknowledges support from the youth scientific laboratory project, topic FEUZ-2020-0038.JWST has ushered in an era of unprecedented ability to characterize exoplanetary atmospheres. While there are over 5000 confirmed planets, more than 4000 Transiting Exoplanet Survey Satellite (TESS) planet candidates are still unconfirmed and many of the best planets for atmospheric characterization may remain to be identified. We present a sample of TESS planets and planet candidates that we identify as “best-in-class” for transmission and emission spectroscopy with JWST. These targets are sorted into bins across equilibrium temperature Teq and planetary radius Rp and are ranked by a transmission and an emission spectroscopy metric (TSM and ESM, respectively) within each bin. We perform cuts for expected signal size and stellar brightness to remove suboptimal targets for JWST. Of the 194 targets in the resulting sample, 103 are unconfirmed TESS planet candidates, also known as TESS Objects of Interest (TOIs). We perform vetting and statistical validation analyses on these 103 targets to determine which are likely planets and which are likely false positives, incorporating ground-based follow-up from the TESS Follow-up Observation Program to aid the vetting and validation process. We statistically validate 18 TOIs, marginally validate 31 TOIs to varying levels of confidence, deem 29 TOIs likely false positives, and leave the dispositions for four TOIs as inconclusive. Twenty-one of the 103 TOIs were confirmed independently over the course of our analysis. We intend for this work to serve as a community resource and motivate formal confirmation and mass measurements of each validated planet. We encourage more detailed analysis of individual targets by the community.Peer reviewe
Do physician outcome judgments and judgment biases contribute to inappropriate use of treatments? Study protocol
<p>Abstract</p> <p>Background</p> <p>There are many examples of physicians using treatments inappropriately, despite clear evidence about the circumstances under which the benefits of such treatments outweigh their harms. When such over- or under- use of treatments occurs for common diseases, the burden to the healthcare system and risks to patients can be substantial. We propose that a major contributor to inappropriate treatment may be how clinicians judge the likelihood of important treatment outcomes, and how these judgments influence their treatment decisions. The current study will examine the role of judged outcome probabilities and other cognitive factors in the context of two clinical treatment decisions: 1) prescription of antibiotics for sore throat, where we hypothesize overestimation of benefit and underestimation of harm leads to over-prescription of antibiotics; and 2) initiation of anticoagulation for patients with atrial fibrillation (AF), where we hypothesize that underestimation of benefit and overestimation of harm leads to under-prescription of warfarin.</p> <p>Methods</p> <p>For each of the two conditions, we will administer surveys of two types (Type 1 and Type 2) to different samples of Canadian physicians. The primary goal of the Type 1 survey is to assess physicians' perceived outcome probabilities (both good and bad outcomes) for the target treatment. Type 1 surveys will assess judged outcome probabilities in the context of a representative patient, and include questions about how physicians currently treat such cases, the recollection of rare or vivid outcomes, as well as practice and demographic details. The primary goal of the Type 2 surveys is to measure the specific factors that drive individual clinical judgments and treatment decisions, using a 'clinical judgment analysis' or 'lens modeling' approach. This survey will manipulate eight clinical variables across a series of sixteen realistic case vignettes. Based on the survey responses, we will be able to identify which variables have the greatest effect on physician judgments, and whether judgments are affected by inappropriate cues or incorrect weighting of appropriate cues. We will send antibiotics surveys to family physicians (300 per survey), and warfarin surveys to both family physicians and internal medicine specialists (300 per group per survey), for a total of 1,800 physicians. Each Type 1 survey will be two to four pages in length and take about fifteen minutes to complete, while each Type 2 survey will be eight to ten pages in length and take about thirty minutes to complete.</p> <p>Discussion</p> <p>This work will provide insight into the extent to which clinicians' judgments about the likelihood of important treatment outcomes explain inappropriate treatment decisions. This work will also provide information necessary for the development of an individualized feedback tool designed to improve treatment decisions. The techniques developed here have the potential to be applicable to a wide range of clinical areas where inappropriate utilization stems from biased judgments.</p
Comparative analysis of the transcriptome across distant species
The transcriptome is the readout of the genome. Identifying common features in it across distant species can reveal fundamental principles. To this end, the ENCODE and modENCODE consortia have generated large amounts of matched RNA-sequencing data for human, worm and fly. Uniform processing and comprehensive annotation of these data allow comparison across metazoan phyla, extending beyond earlier within-phylum transcriptome comparisons and revealing ancient, conserved features. Specifically, we discover co-expression modules shared across animals, many of which are enriched in developmental genes. Moreover, we use expression patterns to align the stages in worm and fly development and find a novel pairing between worm embryo and fly pupae, in addition to the embryo-to-embryo and larvae-to-larvae pairings. Furthermore, we find that the extent of non-canonical, non-coding transcription is similar in each organism, per base pair. Finally, we find in all three organisms that the gene-expression levels, both coding and non-coding, can be quantitatively predicted from chromatin features at the promoter using a 'universal model' based on a single set of organism-independent parameters
Quantitative 18F-AV1451 Brain Tau PET Imaging in Cognitively Normal Older Adults, Mild Cognitive Impairment, and Alzheimer's Disease Patients
Recent developments of tau Positron Emission Tomography (PET) allows assessment of regional neurofibrillary tangles (NFTs) deposition in human brain. Among the tau PET molecular probes, 18F-AV1451 is characterized by high selectivity for pathologic tau aggregates over amyloid plaques, limited non-specific binding in white and gray matter, and confined off-target binding. The objectives of the study are (1) to quantitatively characterize regional brain tau deposition measured by 18F-AV1451 PET in cognitively normal older adults (CN), mild cognitive impairment (MCI), and AD participants; (2) to evaluate the correlations between cerebrospinal fluid (CSF) biomarkers or Mini-Mental State Examination (MMSE) and 18F-AV1451 PET standardized uptake value ratio (SUVR); and (3) to evaluate the partial volume effects on 18F-AV1451 brain uptake.Methods: The study included total 115 participants (CN = 49, MCI = 58, and AD = 8) from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Preprocessed 18F-AV1451 PET images, structural MRIs, and demographic and clinical assessments were downloaded from the ADNI database. A reblurred Van Cittertiteration method was used for voxelwise partial volume correction (PVC) on PET images. Structural MRIs were used for PET spatial normalization and region of interest (ROI) definition in standard space. The parametric images of 18F-AV1451 SUVR relative to cerebellum were calculated. The ROI SUVR measurements from PVC and non-PVC SUVR images were compared. The correlation between ROI 18F-AV1451 SUVR and the measurements of MMSE, CSF total tau (t-tau), and phosphorylated tau (p-tau) were also assessed.Results:18F-AV1451 prominently specific binding was found in the amygdala, entorhinal cortex, parahippocampus, fusiform, posterior cingulate, temporal, parietal, and frontal brain regions. Most regional SUVRs showed significantly higher uptake of 18F-AV1451 in AD than MCI and CN participants. SUVRs of small regions like amygdala, entorhinal cortex and parahippocampus were statistically improved by PVC in all groups (p < 0.01). Although there was an increasing tendency of 18F-AV-1451 SUVRs in MCI group compared with CN group, no significant difference of 18F-AV1451 deposition was found between CN and MCI brains with or without PVC (p > 0.05). Declined MMSE score was observed with increasing 18F-AV1451 binding in amygdala, entorhinal cortex, parahippocampus, and fusiform. CSF p-tau was positively correlated with 18F-AV1451 deposition. PVC improved the results of 18F-AV-1451 tau deposition and correlation studies in small brain regions.Conclusion: The typical deposition of 18F-AV1451 tau PET imaging in AD brain was found in amygdala, entorhinal cortex, fusiform and parahippocampus, and these regions were strongly associated with cognitive impairment and CSF biomarkers. Although more deposition was observed in MCI group, the 18F-AV-1451 PET imaging could not differentiate the MCI patients from CN population. More tau deposition related to decreased MMSE score and increased level of CSF p-tau, especially in ROIs of amygdala, entorhinal cortex and parahippocampus. PVC did improve the results of tau deposition and correlation studies in small brain regions and suggest to be routinely used in 18F-AV1451 tau PET quantification
Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19
IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19.
Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19.
DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022).
INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days.
MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes.
RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively).
CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes.
TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570
The effects of a 6-month Schroth intervention for Adolescent Idiopathic Scoliosis (AIS): preliminary analysis of an ongoing randomized controlled trial
The effects of a 6-month Schroth intervention for Adolescent Idiopathic Scoliosis (AIS): preliminary analysis of an ongoing randomized controlled trial
Schroth Physiotherapeutic Scoliosis-Specific Exercises Added to the Standard of Care Lead to Better Cobb Angle Outcomes in Adolescents with Idiopathic Scoliosis – an Assessor and Statistician Blinded Randomized Controlled Trial
<div><p>Background</p><p>The North American non-surgical standard of care for adolescent idiopathic scoliosis (AIS) includes observation and bracing, but not exercises. Schroth physiotherapeutic scoliosis-specific exercises (PSSE) showed promise in several studies of suboptimal methodology. The Scoliosis Research Society calls for rigorous studies supporting the role of exercises before including it as a treatment recommendation for scoliosis.</p><p>Objectives</p><p>To determine the effect of a six-month Schroth PSSE intervention added to standard of care (Experimental group) on the Cobb angle compared to standard of care alone (Control group) in patients with AIS.</p><p>Methods</p><p>Fifty patients with AIS aged 10–18 years, with curves of 10°-45° and Risser grade 0–5 were recruited from a single pediatric scoliosis clinic and randomized to the Experimental or Control group. Outcomes included the change in the Cobb angles of the Largest Curve and Sum of Curves from baseline to six months. The intervention consisted of a 30–45 minute daily home program and weekly supervised sessions. Intention-to-treat and per protocol linear mixed effects model analyses are reported.</p><p>Results</p><p>In the intention-to-treat analysis, after six months, the Schroth group had significantly smaller Largest Curve than controls (-3.5°, 95% CI -1.1° to -5.9°, <i>p</i> = 0.006). Likewise, the between-group difference in the square root of the Sum of Curves was -0.40°, (95% CI -0.03° to -0.8°, <i>p</i> = 0.046), suggesting that an average patient with 51.2° at baseline, will have a 49.3° Sum of Curves at six months in the Schroth group, and 55.1° in the control group with the difference between groups increasing with severity. Per protocol analyses produced similar, but larger differences: Largest Curve = -4.1° (95% CI -1.7° to -6.5°, <i>p</i> = 0.002) and (95% CI -0.8 to 0.2, <i>p</i> = 0.006).</p><p>Conclusion</p><p>Schroth PSSE added to the standard of care were superior compared to standard of care alone for reducing the curve severity in patients with AIS.</p><p>Trial Registration</p><p><a href="https://clinicaltrials.gov/ct2/show/NCT01610908" target="_blank">NCT01610908</a></p></div
Linear mixed effects model coefficients and significance values in the intention-to-treat and the per protocol analyses with 95% confidence intervals;.
<p>Linear mixed effects model coefficients and significance values in the intention-to-treat and the per protocol analyses with 95% confidence intervals;.</p
Baseline characteristics of the study population.
<p>Baseline characteristics of the study population.</p