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We present measurements of the radial profiles of the mass and galaxy number density around Sunyaev–Zel’dovich (SZ)-selected clusters using both weak lensing and galaxy counts. The clusters are selected from the Atacama Cosmology Telescope Data Release 5 and the galaxies from the Dark Energy Survey Year 3 data set. With signal-to-noise ratio of 62 (45) for galaxy (weak lensing) profiles over scales of about 0.2–20 h-1 Mpc, these are the highest precision measurements for SZ-selected clusters to date. Because SZ selection closely approximates mass selection, these measurements enable several tests of theoretical models of the mass and light distribution around clusters. Our main findings are: (1) The splashback feature is detected at a consistent location in both the mass and galaxy profiles and its location is consistent with predictions of cold dark matter N-body simulations. (2) The full mass profile is also consistent with the simulations. (3) The shapes of the galaxy and lensing profiles are remarkably similar for our sample over the entire range of scales, from well inside the cluster halo to the quasilinear regime. We measure the dependence of the profile shapes on the galaxy sample, redshift, and cluster mass. We extend the Diemer & Kravtsov model for the cluster profiles to the linear regime using perturbation theory and show that it provides a good match to the measured profiles. We also compare the measured profiles to predictions of the standard halo model and simulations that include hydrodynamics. Applications of these results to cluster mass estimation, cosmology, and astrophysics are discussed.

We present measurements of the average thermal Sunyaev Zel’dovich (tSZ) effect from optically selected galaxy groups and clusters at high signal-to-noise (up to ) and estimate their baryon content within a radius aperture. Sources from the Sloan Digital Sky Survey Baryon Oscillation Spectroscopic Survey DR15 catalog overlap with 3,700 sq deg of sky observed by the Atacama Cosmology Telescope (ACT) from 2008 to 2018 at 150 and 98 GHz (ACT DR5), and 2,089 sq deg of internal linear combination component-separated maps combining ACT and Planck data (ACT DR4). The corresponding optical depths , which depend on the baryon content of the halos, are estimated using results from cosmological hydrodynamic simulations assuming an active galactic nuclei feedback radiative cooling model. We estimate the mean mass of the halos in multiple luminosity bins, and compare the tSZ-based estimates to theoretical predictions of the baryon content for a Navarro-Frenk-White profile. We do the same for estimates extracted from fits to pairwise baryon momentum measurements of the kinematic Sunyaev-Zel’dovich effect (kSZ) for the same dataset obtained in a companion paper. We find that the estimates from the tSZ measurements in this work and the kSZ measurements in the companion paper agree within for two out of the three disjoint luminosity bins studied, while they differ by in the highest luminosity bin. The optical depth estimates account for one-third to all of the theoretically predicted baryon content in the halos across luminosity bins. Potential systematic uncertainties are discussed. The tSZ and kSZ measurements provide a step toward empirical Compton- relationships to provide new tests of cluster formation and evolution models.

We present a detection of the pairwise kinematic Sunyaev-Zeldovich (kSZ) effect using Atacama Cosmology Telescope (ACT) and Planck CMB observations in combination with Luminous Red Galaxy samples from the Sloan Digital Sky Survey (SDSS) DR15 catalog. Results are obtained using three ACT CMB maps: co-added 150 and 98 GHz maps, combining observations from 2008-2018 (ACT DR5), which overlap with SDSS DR15 over 3,700 sq. deg., and a component-separated map using night-time only observations from 2014-2015 (ACT DR4), overlapping with SDSS DR15 over 2,089 sq. deg. Comparisons of the results from these three maps provide consistency checks in relation to potential frequency-dependent foreground contamination. A total of 343,647 galaxies are used as tracers to identify and locate galaxy groups and clusters from which the kSZ signal is extracted using aperture photometry. We consider the impact of various aperture photometry assumptions and covariance estimation methods on the signal extraction. Theoretical predictions of the pairwise velocities are used to obtain best-fit, mass-averaged, optical depth estimates for each of five luminosity-selected tracer samples. A comparison of the kSZ-derived optical depth measurements obtained here to those derived from the thermal SZ effect for the same sample is presented in a companion paper.

Two recent large data releases for the Atacama Cosmology Telescope (ACT), called DR4 and DR5, are available for public access. These data include temperature and polarization maps that cover nearly half the sky at arcminute resolution in three frequency bands; lensing maps and component-separated maps covering ~2100 deg2 of sky; derived power spectra and cosmological likelihoods; a catalog of over 4000 galaxy clusters; and supporting ancillary products including beam functions and masks. The data and products are described in a suite of ACT papers; here we provide a summary. In order to facilitate ease of access to these data, we present a set of Jupyter IPython notebooks developed to introduce users to DR4, DR5, and the tools needed to analyze these data. The data products (excluding simulations) and the set of notebooks are publicly available on the NASA Legacy Archive for Microwave Background Data Analysis; simulation products are available on the National Energy Research Scientific Computing Center.

The scattering of cosmic microwave background (CMB) photons off the free-electron gas in galaxies and clusters leaves detectable imprints on high resolution CMB maps: the thermal and kinematic Sunyaev-Zel'dovich effects (tSZ and kSZ respectively). We use combined microwave maps from the Atacama Cosmology Telescope DR5 and Planck in combination with the CMASS (mean redshift ⟨z

We present a catalog of 4195 optically confirmed Sunyaev–Zel’dovich (SZ) selected galaxy clusters detected with signal-to-noise ratio >4 in 13,211 deg2 of sky surveyed by the Atacama Cosmology Telescope (ACT). Cluster candidates were selected by applying a multifrequency matched filter to 98 and 150 GHz maps constructed from ACT observations obtained from 2008 to 2018 and confirmed using deep, wide-area optical surveys. The clusters span the redshift range 0.04 < z < 1.91 (median z = 0.52). The catalog contains 222 z > 1 clusters, and a total of 868 systems are new discoveries. Assuming an SZ signal versus mass-scaling relation calibrated from X-ray observations, the sample has a 90% completeness mass limit of M500c > 3.8 × 1014 Me, evaluated at z = 0.5, for clusters detected at signal-to-noise ratio >5 in maps filtered at an angular scale of 2 4. The survey has a large overlap with deep optical weak-lensing surveys that are being used to calibrate the SZ signal mass-scaling relation, such as the Dark Energy Survey (4566 deg2), the Hyper Suprime-Cam Subaru Strategic Program (469 deg2), and the Kilo Degree Survey (825 deg2). We highlight some noteworthy objects in the sample, including potentially projected systems, clusters with strong lensing features, clusters with active central galaxies or star formation, and systems of multiple clusters that may be physically associated. The cluster catalog will be a useful resource for future cosmological analyses and studying the evolution of the intracluster medium and galaxies in massive clusters over the past 10 Gyr.

We present ΛCDM cosmological parameter constraints obtained from delensed microwave background power spectra. Lensing maps from a subset of DR4 data from the Atacama Cosmology Telescope (ACT) are used to undo the lensing effect in ACT spectra observed at 150 and 98 GHz. At 150 GHz, we remove the lensing distortion with an effective efficiency of 30% (TT), 30% (EE), 26% (TE) and 20% (BB); this results in detections of the delensing effect at 8.7σ (TT), 5.1σ (EE), 2.6σ (TE), and 2.4σ (BB) significance. The combination of 150 and 98 GHz TT, EE, and TE delensed spectra is well fit by a standard ΛCDM model. We also measure the shift in best-fit parameters when fitting delensed versus lensed spectra; while this shift does not inform our ability to measure cosmological parameters, it does provide a three-way consistency check among the lensing inferred from the best-fit parameters, the lensing in the CMB power spectrum, and the reconstructed lensing map. This shift is predicted to be zero when fitting with the correct model since both lensed and delensed spectra originate from the same region of sky. Fitting with a ΛCDM model and marginalizing over foregrounds, we find that the shift in cosmological parameters is consistent with zero. Our results show that gravitational lensing of the microwave background is internally consistent within the framework of the standard cosmological model.

We construct cosmic microwave background lensing mass maps using data from the 2014 and 2015 seasons of observations with the Atacama Cosmology Telescope (ACT). These maps cover 2100 square degrees of sky and overlap with a wide variety of optical surveys. The maps are signal dominated on large scales and have fidelity such that their correlation with the cosmic infrared background is clearly visible by eye. We also create lensing maps with thermal Sunyaev-Zel'dovich contamination removed using a novel cleaning procedure that only slightly degrades the lensing signal-to-noise ratio. The cross-spectrum between the cleaned lensing map and the BOSS CMASS galaxy sample is detected at 10σ significance, with an amplitude of A = 1.02 ± 0.10 relative to the Planck best-fitting Lambda cold dark matter cosmological model with fiducial linear galaxy bias. Our measurement lays the foundation for lensing cross-correlation science with current ACT data and beyond.

We present new arcminute-resolution maps of the Cosmic Microwave Background temperature and polarization anisotropy from the Atacama Cosmology Telescope, using data taken from 2013–2016 at 98 and 150 GHz. The maps cover more than 17,000 deg2, the deepest 600 deg2 with noise levels below 10µK-arcmin. We use the power spectrum derived from almost 6,000 deg2 of these maps to constrain cosmology. The ACT data enable a measurement of the angular scale of features in both the divergence-like polarization and the temperature anisotropy, tracing both the velocity and density at last-scattering. From these one can derive the distance to the last-scattering surface and thus infer the local expansion rate, H0. By combining ACT data with large-scale information from WMAP we measure H0 = 67.6±1.1 km/s/Mpc, at 68% confidence, in excellent agreement with the independently-measured Planck satellite estimate (from ACT alone we find H0 = 67.9 ± 1.5 km/s/Mpc). The ΛCDM model provides a good fit to the ACT data, and we find no evidence for deviations: both the spatial curvature, and the departure from the standard lensing signal in the spectrum, are zero to within 1σ; the number of relativistic species, the primordial Helium fraction, and the running of the spectral index are consistent with ΛCDM predictions to within 1.5–2.2σ. We compare ACT, WMAP, and Planck at the parameter level and find good consistency; we investigate how the constraints on the correlated spectral index and baryon density parameters readjust when adding CMB large-scale information that ACT does not measure. The DR4 products presented here will be publicly released on the NASA Legacy Archive for Microwave Background Data Analysis.

We present the temperature and polarization angular power spectra of the CMB measured by the Atacama Cosmology Telescope (ACT) from 5400 deg2 of the 2013–2016 survey, which covers >15000 deg2 at 98 and 150 GHz. For this analysis we adopt a blinding strategy to help avoid confirmation bias and, related to this, show numerous checks for systematic error done before unblinding. Using the likelihood for the cosmological analysis we constrain secondary sources of anisotropy and foreground emission, and derive a “CMB-only” spectrum that extends to ` = 4000. At large angular scales, foreground emission at 150 GHz is ∼1% of TT and EE within our selected regions and consistent with that found by Planck. Using the same likelihood, we obtain the cosmological parameters for ΛCDM for the ACT data alone with a prior on the optical depth of τ = 0.065 ± 0.015. ΛCDM is a good fit. The best-fit model has a reduced χ2 of 1.07 (PTE = 0.07) with H0 = 67.9 ± 1.5 km/s/Mpc. We show that the lensing BB signal is consistent with ΛCDM and limit the celestial EB polarization angle to ψP = −0.07◦ ±0.09◦. We directly cross correlate ACT with Planck and observe generally good agreement but with some discrepancies in TE. All data on which this analysis is based will be publicly released.

We use gravitational lensing of the cosmic microwave background (CMB) to measure the mass of the most distant blindly selected sample of galaxy clusters on which a lensing measurement has been performed to date. In CMB data from the the Atacama Cosmology Telescope and the Planck satellite, we detect the stacked lensing effect from 677 near-infrared-selected galaxy clusters from the Massive and Distant Clusters of WISE Survey (MaDCoWS), which have a mean redshift of zñ = 1.08. There are currently no representative optical weak lensing measurements of clusters that match the distance and average mass of this sample. We detect the lensing signal with a significance of 4.2s. We model the signal with a halo model framework to find the mean mass of the population from which these clusters are drawn. Assuming that the clusters follow Navarro–Frenk–White (NFW) density profiles, we infer a mean mass of M500cñ = (1.7 + 0.4) ´ 1014 M*. We consider systematic uncertainties from cluster redshift errors, centering errors, and the shape of the NFW profile. These are all smaller than 30% of our reported uncertainty. This work highlights the potential of CMB lensing to enable cosmological constraints from the abundance of distant clusters populating ever larger volumes of the observable universe, beyond the capabilities of optical weak lensing measurements.

Optimal analyses of many signals in the cosmic microwave background (CMB) require map-level extraction of individual components in the microwave sky, rather than measurements at the power spectrum level alone. To date, nearly all map-level component separation in CMB analyses has been performed exclusively using satellite data. In this paper, we implement a component separation method based on the internal linear combination (ILC) approach which we have designed to optimally account for the anisotropic noise (in the 2D Fourier domain) often found in ground-based CMB experiments. Using this method, we combine multifrequency data from the Planck satellite and the Atacama Cosmology Telescope Polarimeter (ACTPol) to construct the first wide-area (≈2100 sq. deg.), arcminute-resolution component-separated maps of the CMB temperature anisotropy and the thermal Sunyaev-Zel'dovich (tSZ) effect sourced by the inverse-Compton scattering of CMB photons off hot, ionized gas. Our ILC pipeline allows for explicit deprojection of various contaminating signals, including a modified blackbody approximation of the cosmic infrared background (CIB) spectral energy distribution. The cleaned CMB maps will be a useful resource for CMB lensing reconstruction, kinematic SZ cross-correlations, and primordial non-Gaussianity studies. The tSZ maps will be used to study the pressure profiles of galaxies, groups, and clusters through cross-correlations with halo catalogs, with dust contamination controlled via CIB deprojection. The data products described in this paper are available on LAMBDA.

We present a detection of the splashback feature around galaxy clusters selected using the Sunyaev-Zel'dovich (SZ) signal. Recent measurements of the splashback feature around optically selected galaxy clusters have found that the splashback radius, rsp, is smaller than predicted by N-body simulations.Apossible explanation for this discrepancy is that rsp inferred from the observed radial distribution of galaxies is affected by selection effects related to the optical cluster-finding algorithms.We test this possibility by measuring the splashback feature in clusters selected via the SZ effect in data from the South Pole Telescope SZ survey and the Atacama Cosmology Telescope Polarimeter survey. The measurement is accomplished by correlating these cluster samples with galaxies detected in the Dark Energy Survey Year 3 data. The SZ observable used to select clusters in this analysis is expected to have a tighter correlation with halo mass and to be more immune to projection effects and aperture-induced biases, potentially ameliorating causes of systematic error for optically selected clusters. We find that the measured rsp for SZ-selected clusters is consistent with the expectations from simulations, although the small number of SZ-selected clusters makes a precise comparison difficult. In agreement with previous work, when using optically selected redMaPPer clusters with similar mass and redshift distributions, rsp is ~2σ smaller than in the simulations. These results motivate detailed investigations of selection biases in optically selected cluster catalogues and exploration of the splashback feature around larger samples of SZ-selected clusters. Additionally, we investigate trends in the galaxy profile and splashback feature as a function of galaxy colour, finding that blue galaxies have profiles close to a power law with no discernible splashback feature, which is consistent with them being on their first infall into the cluster.

We present the temperature and polarization angular power spectra measured by the Atacama Cosmology Telescope Polarimeter (ACTPol). We analyze night-time data collected during 2013-14 using two detector arrays at 149 GHz, from 548 deg2 of sky on the celestial equator. We use these spectra, and the spectra measured with the MBAC camera on ACT from 2008-10, in combination with planck and wmap data to estimate cosmological parameters from the temperature, polarization, and temperature-polarization cross-correlations. We find the new ACTPol data to be consistent with the ΛCDM model. The ACTPol temperature-polarization cross-spectrum now provides stronger constraints on multiple parameters than the ACTPol temperature spectrum, including the baryon density, the acoustic peak angular scale, and the derived Hubble constant. The new ACTPol data provide information on damping tail parameters. The joint uncertainty on the number of neutrino species and the primordial helium fraction is reduced by 20% when adding ACTPol to Planck temperature data alone.

We use microwave temperature maps from two seasons of data from the Atacama Cosmology Telescope at 146 GHz, together with the "Constant Mass" CMASS galaxy sample from the Baryon Oscillation Spectroscopic Survey to measure the kinematic Sunyaev-Zel'dovich (kSZ) effect over the redshift range z=0.4-0.7. We use galaxy positions and the continuity equation to obtain a reconstruction of the line-of-sight velocity field. We stack the microwave temperature at the location of each halo, weighted by the corresponding reconstructed velocity. We vary the size of the aperture photometry filter used, thus probing the free electron profile of these halos from within the virial radius out to three virial radii, on the scales relevant for investigating the missing baryons problem. The resulting best fit kSZ model is preferred over the no-kSZ hypothesis at 3.3 and 2.9σ for two independent velocity reconstruction methods, using 25,537 galaxies over 660 square degrees. The data suggest that the baryon profile is shallower than the dark matter in the inner regions of the halos probed here, potentially due to energy injection from active galactic nucleus or supernovae. Thus, by constraining the gas profile on a wide range of scales, this technique will be useful for understanding the role of feedback in galaxy groups and clusters. The effect of foregrounds that are uncorrelated with the galaxy velocities is expected to be well below our signal, and residual thermal Sunyaev-Zel'dovich contamination is controlled by masking the most massive clusters. Finally, we discuss the systematics involved in converting our measurement of the kSZ amplitude into the mean free electron fraction of the halos in our sample.

Fluctuations in the intensity and polarization of the cosmic microwave background (CMB) and the large-scale distribution of matter in the universe each contain clues about the nature of the earliest moments of time. The next generation of CMB and large-scale structure (LSS) experiments are poised to test the leading paradigm for these earliest moments-the theory of cosmic inflation-and to detect the imprints of the inflationary epoch, thereby dramatically increasing our understanding of fundamental physics and the early universe. A future CMB experiment with sufficient angular resolution and frequency coverage that surveys at least 1% of the sky to a depth of 1 uK-arcmin can deliver a constraint on the tensor-to-scalar ratio that will either result in a 5σ measurement of the energy scale of inflation or rule out all large-field inflation models, even in the presence of foregrounds and the gravitational lensing B-mode signal. LSS experiments, particularly spectroscopic surveys such as the Dark Energy Spectroscopic Instrument, will complement the CMB effort by improving current constraints on running of the spectral index by up to a factor of four, improving constraints on curvature by a factor of ten, and providing non-Gaussianity constraints that are competitive with the current CMB bounds.

This is a report on the status and prospects of the quantification of neutrino properties through the cosmological neutrino background for the Cosmic Frontier of the Division of Particles and Fields Community Summer Study long-term planning exercise. Experiments planned and underway are prepared to study the cosmological neutrino background in detail via its influence on distance-redshift relations and the growth of structure. The program for the next decade described in this document, including upcoming spectroscopic galaxy surveys eBOSS and DESI and a new Stage-IV CMB polarization experiment CMB-S4, will achieve σ(σmν) = 16 meV and σ(Neff) = 0.020. Such a mass measurement will produce a high significance detection of non-zero σmν, whose lower bound derived from atmospheric and solar neutrino oscillation data is about 58 meV. If neutrinos have a minimal normal mass hierarchy, this measurement will definitively rule out the inverted neutrino mass hierarchy, shedding light on one of the most puzzling aspects of the Standard Model of particle physics - the origin of mass. This precise a measurement of Neff will allow for high sensitivity to any light and dark degrees of freedom produced in the big bang and a precision test of the standard cosmological model prediction that Neff = 3.046.

Daniel G Whitney,1 Edward A Hurvitz,1 Jennifer M Ryan,2,3 Maureen J Devlin,4 Michelle S Caird,5 Zachary P French,1 Elie C Ellenberg,1 Mark D Peterson1 1Department of Physical Medicine and Rehabilitation, Michigan Medicine, University of Michigan, Ann Arbor, MI, USA; 2Department of Epidemiology and Public Health Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland; 3Department of Clinical Sciences, Brunel University London, Uxbridge, UK; 4Department of Anthropology, University of Michigan, Ann Arbor, MI, USA; 5Department of Orthopedic Surgery, Michigan Medicine, University of Michigan, Ann Arbor, MI, USA Purpose: Individuals with cerebral palsy (CP) are at increased risk for frailty and chronic disease due to factors experienced throughout the lifespan, such as excessive sedentary behaviors and malnutrition. However, little is known about noncommunicable diseases (NCDs) and multimorbidity profiles in young adults with CP. The study objective was to compare NCD and multimorbidity profiles between young adults with and without CP.Methods: A clinic-based sample of adults (18–30 years) with (n=452) and without (n=448) CP was examined at the University of Michigan Medical Center. The prevalence and predictors of 13 NCDs were evaluated, including existing diagnoses or historical record of musculoskeletal, cardiometabolic, and pulmonary morbidities. The level of motor impairment was determined by the Gross Motor Function Classification System (GMFCS) and stratified by less vs more severe motor impairment (GMFCS I–III vs IV–V). Logistic regression was used to determine the odds of NCD morbidity and multimorbidity in adults with CP compared to adults without CP, and for GMFCS IV–V compared to GMFCS I–III in those with CP, after adjusting for age, sex, body mass index, and smoking.Results: Adults with CP had a higher prevalence of osteopenia, osteoporosis, hypertension, myocardial infarction, hyperlipidemia, asthma, and multimorbidity compared to adults without CP, and higher odds of musculoskeletal (odds ratio [OR]: 6.97) and cardiometabolic morbidity (OR: 1.98), and multimorbidity (OR: 2.67). Adults with CP with GMFCS levels IV–V had a higher prevalence of osteopenia/osteoporosis, osteoarthritis, hypertension, other cardiovascular conditions, pulmonary embolism, and multimorbidity, and higher odds of musculoskeletal (OR: 3.41), cardiometabolic (OR: 2.05), pulmonary morbidity (OR: 1.42), and multimorbidity (OR: 3.45) compared to GMFCS I–III.Conclusion: Young adults with CP have a higher prevalence of chronic NCDs and multimorbidity compared to young adults without CP, which is pronounced in those with more severe motor impairment. These findings reiterate the importance of early screening for prevention of NCDs in CP. Keywords: cerebral palsy, noncommunicable disease, multimorbidity, osteoporosis, osteoarthritis, cardiovascular disease, diabetes, pulmonary disease

Rationale We propose narrative evidence-based medicine as a necessary elaboration of the NIH translational research roadmap. The roadmap defined two complex obstacles, T1 and T2, to the progress of research from the 'bench' or basic laboratory science to the 'bedside' or clinical application, the traversal of which requires emergence of complex transformative relationships between the parties and stakeholders. It fails to encompass patient interactions, hesitancies and alliances with medical care.Aims and Objectives We suggest a third transformative or translational step, T3, that begins at the point that practitioners have themselves elected to adopt and recommend strategies and interventions based on high-level evidence and guidelines. In our model, T3 encompasses all aspects of care that converge on the practitionerDSpatient relationship and ultimately determine what therapies and choices patients actually make regarding their care.Results Learning from the biopsychosocial model, patient-centred care and shared decision making while attending to the ethical injunction of Emmanuel Levinas to know the other, we have developed a medical practice and theory that unites the local and specific concerns of narrative medicine with the generalizability and power of evidence-based medicine.Conclusions We offer innovative approaches to study, teach and improve the therapeutic intimacy and integrative effectiveness of the practitioner-patient relationship. [ABSTRACT FROM AUTHOR]

Context: Antidepressant medication is frequently prescribed for patients with anorexia nervosa.Objective: To determine whether fluoxetine can promote recovery and prolong time-to-relapse among patients with anorexia nervosa following weight restoration.Design, Setting, and Participants: Randomized, double-blind, placebo-controlled trial. From January 2000 until May 2005, 93 patients with anorexia nervosa received intensive inpatient or day-program treatment at the New York State Psychiatric Institute or Toronto General Hospital. Participants regained weight to a minimum body mass index (calculated as weight in kilograms divided by the square of height in meters) of 19.0 and were then eligible to participate in the randomized phase of the trial.Interventions: Participants were randomly assigned to receive fluoxetine or placebo and were treated for up to 1 year as outpatients in double-blind fashion. All patients also received individual cognitive behavioral therapy.Main Outcome Measures: The primary outcome measures were time-to-relapse and the proportion of patients successfully completing 1 year of treatment.Results: Forty-nine patients were assigned to fluoxetine and 44 to placebo. Similar percentages of patients assigned to fluoxetine and to placebo maintained a body mass index of at least 18.5 and remained in the study for 52 weeks (fluoxetine, 26.5%; placebo, 31.5%; P = .57). In a Cox proportional hazards analysis, with prerandomization body mass index, site, and diagnostic subtype as covariates, there was no significant difference between fluoxetine and placebo in time-to-relapse (hazard ratio, 1.12; 95% CI, 0.65-2.01; P = .64).Conclusions: This study failed to demonstrate any benefit from fluoxetine in the treatment of patients with anorexia nervosa following weight restoration. Future efforts should focus on developing new models to understand the persistence of this illness and on exploring new psychological and pharmacological treatment approaches.Trial Registration: clinicaltrials.gov Identifier: NCT00288574. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This open clinical trial examined the efficacy of treating obese patients with binge eating disorder (BED) with phentermine and fluoxetine in the setting of cognitive-behavioral therapy (CBT). METHOD: Sixteen obese women received individual CBT along with phentermine/fluoxetine. Treatment goals included elimination of binge eating, weight loss, and reduced psychological distress. Following active treatment, patients were offered once-monthly maintenance treatment for 3 years. RESULTS: Patients showed significant reduction in binge frequency, weight loss, and psychological distress at the end of active treatment, but regained most of the weight within 1 year. At 18-month follow-up, there was an ongoing reduction in binge eating for patients who continued maintenance. DISCUSSION: Treatment produced comparable binge suppression and more weight loss than most reported studies of CBT alone. However, there is significant weight regain, particularly following medication discontinuation. This study does not support the long-term clinical utility of adding phentermine/fluoxetine to CBT for BED. Copyright 2000 by John Wiley & Sons, Inc. [ABSTRACT FROM AUTHOR]

OBJECTIVE: While most individuals with bulimia nervosa begin dieting prior to the onset of binge eating, some individuals begin binge eating prior to dieting. The purpose of this study was to assess the differences between these two groups. METHODS: Participants (N = 120) in a treatment study for bulimia nervosa were separated into two groups (Binge First vs. Diet First) based on the ages they reported for the onset of binge eating and of dieting and then compared across a number of variables. RESULTS: Individuals in the Binge First group reported higher weight, higher shape and weight concern, lower age of onset of eating disorder symptoms, and an altered relationship of binge eating to vomiting when compared to individuals in the Diet First group. DISCUSSION: The differences between the two groups suggest that there may be subgroups of individuals with purging bulimia nervosa and that individuals in the Binge First group more closely resemble individuals with binge eating disorder than do those in the Diet First group. [ABSTRACT FROM AUTHOR]

Objective: To revisit the merits and problems inherent in considering obesity, or some aspect of obesity, as a mental or behavioral disorder. Method: The author suggests shifting the focus from the state of obesity to the process of nonhomeostatic overeating that results in obesity. Studies are reviewed that pertain to various models of nonnormative overeating including eating disorder models that stress the form of overeating, substance use disorder models focusing on its consequences, and affect regulation or stress response models focusing on its function. Results: Studies focusing on abnormal eating patterns, including binge eating and night eating suggest that such patterns may be related to the development of obesity. While the literature pertaining to substance use and other models of nonhomeostatic overeating is beginning to mount, current evidence is mostly preliminary and indirect. Conclusion: An attempt to devise diagnostic criteria based on the above models raises multiple difficulties, since the phenomena central to each model are dimensional, common, and variably associated with distress or dysfunction. A detailed understanding of the neurobiological relationships among eating behavior, reward systems, and affect regulation systems will enable a more meaningful consideration of these models and will facilitate specific treatment for disorders of overeating. © 2007 by Wiley Periodicals, Inc. Int J Eat Disord 2007 [ABSTRACT FROM AUTHOR]

Background: Ethnic and socioeconomic disparities in cancer outcomes are exacerbated by clinical trial underrepresentation. This study aims to identify inequalities in ethnicity and socioeconomic features among ovarian cancer clinical trial participants in two London cancer centres., Methods: All ovarian cancer patients treated between 2017 and 2022 were included. Patients participating in clinical trials were classified as the trial population (TP); the remainder were considered the non-trial population (NTP). Data on disease characteristics and sociodemographic features, including ethnicity and Indices of Multiple Deprivation (IMD) deciles, were accessed from electronic patient records., Results: Of the 892 patients, 212 (24%) were enrolled in trials: 87 in Phase II, 103 in Phase III, and 21 in prospective, non-investigational medicinal product trials. The TP were more likely to be of White ethnicity (72.6% vs. 57.5%; p < 0.001), younger (mean age 58 vs. 60; p = 0.003), living in less deprived areas (most deprived tercile: 21.2% vs. 34.0%; p = 0.004), and English-speaking (95.8% vs. 90.9%; p = 0.041). In the multivariate analysis, White ethnicity ( p < 0.0001), age ( p = 0.003), IMD decile ( p = 0.007), and interpreter requirement ( p = 0.037) were independent predictors of trial participation., Conclusions: Ethnic and socioeconomic inequalities affect trial participation, potentially worsening health disparities in ovarian cancer patients. Strategies to overcome trial recruitment barriers for underserved groups are needed to improve the equity of care.

Background: Intravenous tenecteplase increases reperfusion in patients with salvageable brain tissue on perfusion imaging and might have advantages over alteplase as a thrombolytic for ischaemic stroke. We aimed to assess the non-inferiority of tenecteplase versus alteplase on clinical outcomes in patients selected by use of perfusion imaging., Methods: This international, multicentre, open-label, parallel-group, randomised, clinical non-inferiority trial enrolled patients from 35 hospitals in eight countries. Participants were aged 18 years or older, within 4·5 h of ischaemic stroke onset or last known well, were not being considered for endovascular thrombectomy, and met target mismatch criteria on brain perfusion imaging. Patients were randomly assigned (1:1) by use of a centralised web server with randomly permuted blocks to intravenous tenecteplase (0·25 mg/kg) or alteplase (0·90 mg/kg). The primary outcome was the proportion of patients without disability (modified Rankin Scale 0-1) at 3 months, assessed via masked review in both the intention-to-treat and per-protocol populations. We aimed to recruit 832 participants to yield 90% power (one-sided alpha=0·025) to detect a risk difference of 0·08, with an absolute non-inferiority margin of -0·03. The trial was registered with the Australian New Zealand Clinical Trials Registry, ACTRN12613000243718, and the European Union Clinical Trials Register, EudraCT Number 2015-002657-36, and it is completed., Findings: Recruitment ceased early following the announcement of other trial results showing non-inferiority of tenecteplase versus alteplase. Between March 21, 2014, and Oct 20, 2023, 680 patients were enrolled and randomly assigned to tenecteplase (n=339) and alteplase (n=341), all of whom were included in the intention-to-treat analysis (multiple imputation was used to account for missing primary outcome data for five patients). Protocol violations occurred in 74 participants, thus the per-protocol population comprised 601 people (295 in the tenecteplase group and 306 in the alteplase group). Participants had a median age of 74 years (IQR 63-82), baseline National Institutes of Health Stroke Scale score of 7 (4-11), and 260 (38%) were female. In the intention-to-treat analysis, the primary outcome occurred in 191 (57%) of 335 participants allocated to tenecteplase and 188 (55%) of 340 participants allocated to alteplase (standardised risk difference [SRD]=0·03 [95% CI -0·033 to 0·10], one-tailed p non-inferiority =0·031). In the per-protocol analysis, the primary outcome occurred in 173 (59%) of 295 participants allocated to tenecteplase and 171 (56%) of 306 participants allocated to alteplase (SRD 0·05 [-0·02 to 0·12], one-tailed p non-inferiority =0·01). Nine (3%) of 337 patients in the tenecteplase group and six (2%) of 340 in the alteplase group had symptomatic intracranial haemorrhage (unadjusted risk difference=0·01 [95% CI -0·01 to 0·03]) and 23 (7%) of 335 and 15 (4%) of 340 died within 90 days of starting treatment (SRD 0·02 [95% CI -0·02 to 0·05])., Interpretation: The findings in our study provide further evidence to strengthen the assertion of the non-inferiority of tenecteplase to alteplase, specifically when perfusion imaging has been used to identify reperfusion-eligible stroke patients. Although non-inferiority was achieved in the per-protocol population, it was not reached in the intention-to-treat analysis, possibly due to sample size limtations. Nonetheless, large-scale implementation of perfusion CT to assist in patient selection for intravenous thrombolysis in the early time window was shown to be feasible., Funding: Australian National Health Medical Research Council; Boehringer Ingelheim., Competing Interests: Declaration of interests MWP is on a Boehringer-Ingelheim Advisory Board for metalyse in stroke. FCN has received grants from the National Health and Medical Research Council of Australia and the National Heart Foundation of Australia. AM participates on an advisory board for Boehringer Ingelheim and is a World Stroke Organisation board member. HSM reports grants from the British Heart Foundation, the Medical Research Council, the Alzheimer's Society, and the Stroke Association UK, and is the editor-in-chief of the World Stroke Organisation journal, International Journal of Stroke. HM has received speaking fees from the Indonesian Stroke Society and reports travel support for investigator meetings. TGP has received speaking fees from Bayer, Boehringer Ingelheim, Pfizer, and BMS. JFA reports consulting fees from Amgen, Medtronic, and BMS-Pfizer, reports speaking fees from Medtronic and BMS–Pfizer, reports travel support from Daiichi–Sankyo, participates on the advisory board for the WE-TRUST trial, and reports research grants from the Spanish Ministry of Science, the European Commission, and Astra Zeneca. RSG has received travel support from Boehringer Ingelheim. SA has received funding from the UK Stroke Clinical Research Network. KSB is in a spousal relationship with an employee of Boehringer Ingelheim and has received speaking fees from Boehringer Ingelheim and AstraZeneca. All other authors report no disclosures., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Treatment options for pre-treated patients with metastatic triple-negative breast cancer (mTNBC) remain limited. This is the first study to assess the real-world safety and efficacy of sacituzumab govitecan (SG) in the UK., Methods: Data was retrospectively collected from 16 tertiary UK cancer centres. Pts had a diagnosis of mTNBC, received at least two prior lines of treatment (with at least one being in the metastatic setting) and received at least one dose of SG., Results: 132 pts were included. Median age was 56 years (28-91). All patients were ECOG performance status (PS) 0-3 (PS0; 39, PS1; 76, PS2; 16, PS3;1). 75% (99/132) of pts had visceral metastases including 18% (24/132) of pts with CNS disease. Median PFS (mPFS) was 5.2 months (95% CI 4.5-6.6) with a median OS (mOS) of 8.7 months (95% CI 6.8-NA). The most common adverse events (AEs) were fatigue (all grade; 82%, G3/4; 14%), neutropenia (all grade; 55%, G3/4; 29%), diarrhoea (all grade; 58%, G3/4, 15%), and nausea (all grade; 38%, G3/4; 3%). SG dose reduction was required in 54% of pts., Conclusion: This study supports significant anti-tumour activity in heavily pre-treated pts with mTNBC. Toxicity data aligns with clinical trial experience., (© 2024. The Author(s).)

Marine coastal waters of Bahrain are under pressure due to human activities and climate change. We used marine monitoring data (2005-2020) from 27 sites to establish baseline conditions and develop standards for assessments of water quality. Five hydrodynamic regions were identified: Oyster Beds, North, West, East, East (Coastal). Data from Oyster Beds sites, likely to be less impacted by human activities, were used to determine baseline conditions. For most parameters, candidate thresholds were based on 50 % and 100 % variation from baseline and 95th percentiles. Comparisons of data against different thresholds showed different outcomes. Overall, results indicate good water quality, with potential concerns in East (Coastal). Trend analyses showed some significant trends in all regions: downward (favourable) for some parameters (e.g. turbidity: North) and upward for others (e.g. nitrate: Oyster Beds, East and East (Coastal)). Future work requires greater understanding around optimum guidelines that protect and mitigate any adverse ecological impacts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Morphological intraspecific variation is due to the balance between skeletal plasticity and genetic constraint on the skeleton. Osteogenic responses to external stimuli, such as locomotion, have been well documented interspecifically across the primate order, but less so at the intraspecific level. Here, we examine the differences in cross-sectional variability of the femur, humerus, radius, and tibia in Pan troglodytes troglodytes versus Gorilla gorilla gorilla. We investigate whether there are sex, species, bone, and trait differences in response to variable body size and locomotion., Materials and Methods: Adult male and female P. t. troglodytes and G. g. gorilla long bones from the Cleveland Museum of Natural History were scanned with a peripheral quantitative computer tomography system. Scans were taken at the midshaft of each bone according to functional bone length. Coefficients of variation were used to provide a size-independent measure of variation. We applied a Bonferroni correction to account for the multiple pairwise tests., Results: There were limited significant differences between males and females, however, females tended to be more variable than males. Variation in Gorilla, when significant, was greater than in Pan, although significant differences were limited. There were no differences between bone variability in male and female Gorilla, and female Pan., Discussion: Increased female variability may be due to more variable locomotor behavior, particularly during periods of pregnancy, lactation, and caring for an offspring compared to consistent locomotion over the life course by males. Body size may be a contributing factor to variability; more work is needed to understand this relationship., (© 2023 Wiley Periodicals LLC.)

Children with bone fragility often exhibit elevated bone marrow lipid levels, which may affect mesenchymal stem cell (MSC) differentiation potential and ultimately bone strength via cell-autonomous and/or non-cell-autonomous factors. Here, we use standard co-culture techniques to study biological effects of bone marrow cell-derived secretome on MSC. Bone marrow was collected during routine orthopedic surgery, and the entire marrow cell preparation, with or without red blood cell (RBC) reduction, was plated at three different densities. Conditioned medium (secretome) was collected after 1, 3, and 7 days. ST2 cells, a murine MSC line, were then cultured in the secretomes. Exposure to the secretomes was associated with reductions of up to 62% in MSC MTT outcomes that depended on the duration of secretome development, as well as marrow cell plating density. Reduced MTT values were not associated with diminished cell number and viability assessed using Trypan Blue exclusion. Expression of pyruvate dehydrogenase kinase 4 was modestly elevated, and β-actin levels were transiently reduced in ST2 cells exposed to secretome formulations that had elicited maximal reductions in MTT outcomes. The findings from this study can inform the design of future experimental studies to examine contributions of cell-autonomous and non-cell-autonomous factors in the bone marrow to MSC differentiation potential, bone formation, and skeletal growth. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research., Competing Interests: The authors declare no conflicts of interest., (© 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.)

Understanding the genomic complexity of high-grade serous ovarian cancer is now essential in guiding patient management, particularly in the first-line setting. Our knowledge in this area has expanded rapidly in recent years, with biomarkers developing in parallel to agents designed to exploit cancer-associated genetic aberrations. In this review we will take stock of the current landscape of genetic testing and look towards the future with developments that aim to refine personalized treatment paradigms and track treatment resistance in real time., Competing Interests: Competing interests: RM: Consultancy from MSD, GSK, AZ, Ellipses, Shionogi, Clovis Oncology and GI Innovation Speaker bureau from Roche, GSK, AZ and Clovis Oncology. Travel grants from AZ and GSK. Trial funding – MSD. M-JD: No disclosures., (© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

The treatment of high-grade serous ovarian cancer and high-grade endometrioid ovarian cancer has seen significant improvements in recent years, with BRCA1/2 and homologous recombination status guiding a personalized approach which has resulted in improved patient outcomes. However, for other epithelial ovarian cancer subtypes, first-line treatment remains unchanged from the platinum-paclitaxel trials of the early 2000s. In this review, we explore novel therapeutic approaches being adopted in the treatment of clear cell, mucinous, carcinosarcoma and low-grade serous ovarian cancer and the biological rational behind them. We discuss why such disparities exist, the challenges faced in conducting dedicated trials in these rarer histologies and look towards new approaches being adopted to overcome them., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2023.)

Introduction and Hypothesis: Human menopause transition and post-menopausal syndrome, driven by reduced ovarian activity and estrogen levels, are associated with an increased risk for symptoms including but not limited to sexual dysfunction, metabolic disease, and osteoporosis. Current treatments are limited in efficacy and may have adverse consequences, so investigation for additional treatment options is necessary. Previous studies have demonstrated that percutaneous tibial nerve stimulation (PTNS) and electro-acupuncture near the tibial nerve are minimally invasive treatments that increase vaginal blood perfusion or serum estrogen in the rat model. We hypothesized that PTNS would protect against harmful reproductive and systemic changes associated with menopause., Methods: We examined the effects of twice-weekly PTNS (0.2 ms pulse width, 20 Hz, 2× motor threshold) under ketamine-xylazine anesthesia in ovariectomized (OVX) female Sprague-Dawley rats on menopause-associated physiological parameters including serum estradiol, body weight, blood glucose, bone health, and vaginal blood perfusion. Rats were split into three groups (n = 10 per group): (1) intact control (no stimulation), (2) OVX control (no stimulation), and (3) OVX stimulation (treatment group)., Results: PTNS did not affect serum estradiol levels, body weight, or blood glucose. PTNS transiently increased vaginal blood perfusion during stimulation for up to 5 weeks after OVX and increased areal bone mineral density and yield load of the right femur (side of stimulation) compared to the unstimulated OVX control., Conclusions: PTNS may ameliorate some symptoms associated with menopause. Additional studies to elucidate the full potential of PTNS on menopause-associated symptoms under different experimental conditions are warranted., (© 2022. The International Urogynecological Association.)

Some patients with advanced clear-cell ovarian cancer (CCOC) respond to immunotherapy; however, little is known about the tumor microenvironment (TME) of this relatively rare disease. Here, we describe a comprehensive quantitative and topographical analysis of biopsies from 45 patients, 9 with Federation Internationale des Gynaecologistes et Obstetristes (FIGO) stage I/II (early CCOC) and 36 with FIGO stage III/IV (advanced CCOC). We investigated 14 immune cell phenotype markers, PD-1 and ligands, and collagen structure and texture. We interrogated a microarray data set from a second cohort of 29 patients and compared the TMEs of ARID1A-wildtype (ARID1Awt) versus ARID1A-mutant (ARID1Amut) disease. We found significant variations in immune cell frequency and phenotype, checkpoint expression, and collagen matrix between the malignant cell area (MCA), leading edge (LE), and stroma. The MCA had the largest population of CD138+ plasma cells, the LE had more CD20+ B cells and T cells, whereas the stroma had more mast cells and αSMA+ fibroblasts. PD-L2 was expressed predominantly on malignant cells and was the dominant PD-1 ligand. Compared with early CCOC, advanced-stage disease had significantly more fibroblasts and a more complex collagen matrix, with microarray analysis indicating "TGFβ remodeling of the extracellular matrix" as the most significantly enriched pathway. Data showed significant differences in immune cell populations, collagen matrix, and cytokine expression between ARID1Awt and ARID1Amut CCOC, which may reflect different paths of tumorigenesis and the relationship to endometriosis. Increased infiltration of CD8+ T cells within the MCA and CD4+ T cells at the LE and stroma significantly associated with decreased overall survival., (©2022 The Authors; Published by the American Association for Cancer Research.)

Objectives: Bone is a dynamic organ under continual turnover influenced by life history stage, energy dynamics, diet, climate, and disease. Bone turnover data have enormous potential in biological anthropology for testing evolutionary and biocultural hypotheses, yet few studies have integrated these biomarkers. In the present article we systematically review the current availability, future viability, and applicability of measuring bone turnover markers (BTMs) in dried blood spot (DBS) samples obtained from finger prick whole blood., Methods: Our review considers clinical and public health relevance, biomarker stability in DBS, assay availability, and cost. We consider biomarkers of bone formation such as osteocalcin (bone matrix protein), PINP (N-terminal propeptide of type I collagen), and alkaline phosphatase (osteoblast enzyme), as well as biomarkers of bone resorption such as CTX (marker of collagen breakdown) and TRACP5b (tartrate-resistant acid phosphatase 5b; osteoclast enzyme)., Results: Two BTMs have been validated for DBS: osteocalcin (formation) and TRACP5b (resorption). Prime candidates for future development are CTX and PINP, the formation and resorption markers used for clinical monitoring of response to osteoporosis treatment., Conclusion: BTMs are a field-friendly technique for longitudinal monitoring of skeletal biology during growth, reproduction and aging, combining minimized risk to study participants with maximized ease of sample storage and transport. This combination allows new insights into the effects of energy availability, disease, and physical activity level on bone, and questions about bone gain and loss across life history and in response to environmental factors; these issues are important in human biology, paleoanthropology, bioarchaeology, and forensic anthropology., (© 2022 The Authors. American Journal of Human Biology published by Wiley Periodicals LLC.)

Background: Psychometric studies of eating disorder measures within bariatric surgery populations are limited., Objectives: To examine the interrater reliability and internal consistency of the Eating Disorder Examination (EDE) among patients before and after bariatric surgery., Setting: Three clinical centers of the Longitudinal Assessment of Bariatric Surgery Research Consortium., Methods: The EDE-Bariatric Surgery Version was administered and audio-recorded by trained interviewers before and at annual assessments after bariatric surgery. Approximately 20% of interviews were randomly selected for rating by a second interviewer. Reliability of the original and brief EDE subscales was examined., Results: Interrater reliability of the EDE subscales ranged from .86-.97 for the original subscales and .83-.95 for brief subscales before surgery, and .90-.98 for the original subscales and .92-.97 for brief subscales after bariatric surgery. Interrater agreement (based on kappa) was almost perfect for overeating and binge-eating behaviors and substantial for loss-of-control eating before surgery. Similar interrater agreements (based on kappa) were observed after surgery for subjective overeating and binge-eating episodes. Internal consistency of the subscale and global scores was variable, ranging from .41-.97., Conclusion: Findings provide support of the interrater reliability of the EDE, albeit with variable internal consistency, before and after bariatric surgery. Despite support for trained raters to reliably assess EDE constructs, variability in internal consistency suggests that further psychometric testing and rigorous scale development of disordered eating may be needed for the bariatric surgery population., (Copyright © 2022 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

We present the design and measured performance of a new carbon fiber strut design that is used in a cryogenically cooled truss for the Simons Observatory small aperture telescope. The truss consists of two aluminum 6061 rings separated by 24 struts. Each strut consists of a central carbon fiber tube fitted with two aluminum end caps. We tested the performance of the strut and truss by (i) cryogenically cycling and destructively pull-testing strut samples, (ii) non-destructively pull-testing the final truss, and (iii) measuring the thermal conductivity of the carbon fiber tubes. We found that the strut strength is limited by the mounting fasteners and the strut end caps, not the epoxy adhesive or the carbon fiber tube. This result is consistent with our numerical predictions. Our thermal measurements suggest that the conductive heat load through the struts (from 4 to 1 K) will be less than 1 mW. This strut design may be a promising candidate for use in other cryogenic support structures.

Intricate links between aquatic animals and their environment expose them to chemical and pathogenic hazards, which can disrupt seafood supply. Here we outline a risk schema for assessing potential impacts of chemical and microbial hazards on discrete subsectors of aquaculture-and control measures that may protect supply. As national governments develop strategies to achieve volumetric expansion in seafood production from aquaculture to meet increasing demand, we propose an urgent need for simultaneous focus on controlling those hazards that limit its production, harvesting, processing, trade and safe consumption. Policies aligning national and international water quality control measures for minimizing interaction with, and impact of, hazards on seafood supply will be critical as consumers increasingly rely on the aquaculture sector to supply safe, nutritious and healthy diets., (© 2022. Crown.)

Nine metals including Al, Cd, Cr, Cu, Fe, Mn, Ni, Pb and Zn were analysed from sediment samples collected from 29 stations since 2007 from Bahraini waters. Within this study, it was investigated whether concentrations of these determinants are at concentrations above internationally established Assessment Criteria (AC). The majority of sites were considered not to pose a toxicological risk in terms of metal contamination. Where breaches occurred, they were mainly from historic samples related to Cr, Cu and Ni contamination. A trend assessment revealed that out of 59 significant trends, 36 were downwards and 23 upwards, indicating that some determinants like Al, Zn and Ni are improving strongly across some sites, whilst areas associated with industrial activity still see some increasing trends for Al, Cd, Pb and Zn., (© 2022. Crown.)

Purpose: It takes many years for trainees to become physicians-so long that their individual journeys through medical school and residency are seldom systematically studied and thus not well understood. Lack of understanding hinders effective support of future physicians' development across traditional time-bound phases of medical education. The authors initiated a longitudinal qualitative study, tracing a cohort of 6 trainees through the same medical school and 6 different residencies. They asked, how do stability and change characterize the lived experience of trainees through time?, Method: From 2010 to 2019, the authors conducted in-depth interviews every 6 to 12 months with 6 trainees, using reflective prompts about formative events and prior interviews. Data were inductively coded and analyzed in an iterative fashion. By scrutinizing data via time-ordered displays of codes, the authors identified 3 patterns of stability and change, particularly related to constructing careers in medicine. The study originated at a private medical school in New York, New York., Results: Patterns in the balance between stability and change were shaped by trainees' career interests. Trainees motivated by stable clinical interests perceived their journey as a "series of stepping-stones." Trainees motivated by evolving clinical interests described disruptive change or "upsets"; however, they were still accommodated by medical education. In contrast, trainees motivated by stable nonclinical (i.e., social science) interests perceived their journey as a "struggle" in residency because of the clinically heavy nature of that phase of training., Conclusions: Based on this descriptive, 9-year study of a small number of trainees, medical education seems to accommodate trainees whose journeys are motivated by clinical interests, even if those clinical interests change through time. Medical education could consider alternatives to time-bound frames of reference and focus on the right time for trainees to integrate clinical and social sciences in medical training., (Copyright © 2020 by the Association of American Medical Colleges.)