Assessing Spns2-dependent S1P Transport as a Prospective Therapeutic Target.

S1P (sphingosine 1-phosphate) receptor modulator (SRM) drugs interfere with lymphocyte trafficking by downregulating lymphocyte S1P receptors. While the immunosuppressive activity of SRM drugs has proved useful in treating autoimmune diseases such as multiple sclerosis, that drug class is beset by on-target liabilities such as initial dose bradycardia. The S1P that binds to cell surface lymphocyte S1P receptors is provided by S1P transporters. Mice born deficient in one of these, spinster homolog 2 (Spns2), are lymphocytopenic and have low lymph S1P concentrations. Such observations suggest that inhibition of Spns2-mediated S1P transport might provide another therapeutically beneficial method to modulate immune cell positioning. We report here results using a novel S1P transport blocker (STB), SLF80821178, to investigate the consequences of S1P transport inhibition in rodents. We found that SLF80821178 is efficacious in a multiple sclerosis model but - unlike the SRM fingolimod - neither decreases heart rate nor compromises lung endothelial barrier function. Notably, although Spns2 null mice have a sensorineural hearing defect, mice treated chronically with SLF80821178 have normal hearing acuity. STBs such as SLF80821178 evoke a dose-dependent decrease in peripheral blood lymphocyte counts, which affords a reliable pharmacodynamic marker of target engagement. However, the maximal reduction in circulating lymphocyte counts in response to SLF80821178 is substantially less than the response to SRMs such as fingolimod (50% vs. 90%) due to a lesser effect on T lymphocyte sub-populations by SLF80821178. Finally, in contrast to results obtained with Spns2 deficient mice, lymph S1P concentrations were not significantly changed in response to administration of STBs at doses that evoke maximal lymphopenia, which indicates that current understanding of the mechanism of action of S1P transport inhibitors is incomplete.

Half-life determination of 215At and 221Ra with high-purity radioactive ion beams.

At CERN-ISOLDE, high-purity radioactive ion beams of 219Fr and 221RaF were investigated with α-decay spectroscopy at the CRIS and ASET experiments in the course of three different experimental campaigns. The half-life of 215At, α-decay daughter of 219Fr, is measured to be 36.3(3)[9]µs, and that of 221Ra was determined to be 26.2(1)[6]s, both of which are well in line with the trends in this region of the nuclear landscape but at odds with some of the reported literature.

Functional neurogenomic responses to acoustic threats, including a heterospecific referential alarm call and its referent, in the auditory forebrain of red-winged blackbirds.

In animal communication, functionally referential alarm calls elicit the same behavioral responses as their referents, despite their typically distinct bioacoustic traits. Yet the auditory forebrain in at least one songbird species, the black-capped chickadee Poecile atricapillus, responds similarly to threat calls and their referent predatory owl calls, as assessed by immediate early gene responses in the secondary auditory forebrain nuclei. Whether and where in the brain such perceptual and cognitive equivalence is processed remains to be understood in most other avian systems. Here, we studied the functional neurogenomic (non-) equivalence of acoustic threat stimuli perception by the red-winged blackbird Agelaius phoeniceus in response to the actual calls of the obligate brood parasitic brown-headed cowbird Molothrus ater and the referential anti-parasitic alarm calls of the yellow warbler Setophaga petechia, upon which the blackbird is known to eavesdrop. Using RNA-sequencing from neural tissue in the auditory lobule (primary and secondary auditory nuclei combined), in contrast to previous findings, we found significant differences in the gene expression profiles of both an immediate early gene, ZENK (egr-1), and other song-system relevant gene-products in blackbirds responding to cowbird vs. warbler calls. In turn, direct cues of threats (including conspecific intruder calls and nest-predator calls) elicited higher ZENK and other differential gene expression patterns compared to harmless heterospecific calls. These patterns are consistent with a perceptual non-equivalence in the auditory forebrain of adult male red-winged blackbirds in response to referential calls and the calls of their referents.

Deformation versus Sphericity in the Ground States of the Lightest Gold Isotopes.

The changes in mean-squared charge radii of neutron-deficient gold nuclei have been determined using the in-source, resonance-ionization laser spectroscopy technique, at the ISOLDE facility (CERN). From these new data, nuclear deformations are inferred, revealing a competition between deformed and spherical configurations. The isotopes ^{180,181,182}Au are observed to possess well-deformed ground states and, when moving to lighter masses, a sudden transition to near-spherical shapes is seen in the extremely neutron-deficient nuclides, ^{176,177,179}Au. A case of shape coexistence and shape staggering is identified in ^{178}Au which has a ground and isomeric state with different deformations. These new data reveal a pattern in ground-state deformation unique to the gold isotopes, whereby, when moving from the heavy to light masses, a plateau of well-deformed isotopes exists around the neutron midshell, flanked by near-spherical shapes in the heavier and lighter isotopes-a trend hitherto unseen elsewhere in the nuclear chart. The experimental charge radii are compared to those from Hartree-Fock-Bogoliubov calculations using the D1M Gogny interaction and configuration mixing between states of different deformation. The calculations are constrained by the known spins, parities, and magnetic moments of the ground states in gold nuclei and show a good agreement with the experimental results.

CyBorD-DARA in Newly Diagnosed Transplant-Eligible Multiple Myeloma: Results from the 16-BCNI-001/CTRIAL-IE 16-02 Study Show High Rates of MRD Negativity at End of Treatment.

The phase 1b 16-BCNI-001/CTRIAL-IE 16-02 CyBorD-DARA trial investigated the combination of Daratumumab with cyclophosphamide, bortezomib and dexamethasone in patients with newly diagnosed multiple myeloma (NDMM), followed by autologous stem cell transplantation and Daratumumab maintenance. CR/sCR rates were 50% after transplant and 62.5% at end of treatment. The overall percentage of patients achieving complete response or better was 77.8%. Progression-free survival rate at end of maintenance was 81.3% and estimated 2-year overall survival was 88.9%. 37.5% of patients demonstrated sustained MRD negativity to a level of 10-5 from transplant to analysis at EOT. In this phase 1b study, we have shown CyBorD-DARA to be an effective and well-tolerated immunomodulatory agent-free regiment in transplant-eligible NDMM.

Nuclear moments of indium isotopes reveal abrupt change at magic number 82.

In spite of the high-density and strongly correlated nature of the atomic nucleus, experimental and theoretical evidence suggests that around particular 'magic' numbers of nucleons, nuclear properties are governed by a single unpaired nucleon1,2. A microscopic understanding of the extent of this behaviour and its evolution in neutron-rich nuclei remains an open question in nuclear physics3-5. The indium isotopes are considered a textbook example of this phenomenon6, in which the constancy of their electromagnetic properties indicated that a single unpaired proton hole can provide the identity of a complex many-nucleon system6,7. Here we present precision laser spectroscopy measurements performed to investigate the validity of this simple single-particle picture. Observation of an abrupt change in the dipole moment at N = 82 indicates that, whereas the single-particle picture indeed dominates at neutron magic number N = 82 (refs. 2,8), it does not for previously studied isotopes. To investigate the microscopic origin of these observations, our work provides a combined effort with developments in two complementary nuclear many-body methods: ab initio valence-space in-medium similarity renormalization group and density functional theory (DFT). We find that the inclusion of time-symmetry-breaking mean fields is essential for a correct description of nuclear magnetic properties, which were previously poorly constrained. These experimental and theoretical findings are key to understanding how seemingly simple single-particle phenomena naturally emerge from complex interactions among protons and neutrons.

Epidemiology and outcomes of primary sclerosing cholangitis: an Australian multicentre retrospective cohort study.

BACKGROUND AND AIMS: Little is known regarding the epidemiology and outcomes of patients with primary sclerosing cholangitis (PSC) in Australia. We, therefore, evaluated the epidemiology and clinical outcomes of PSC in a large cohort of Australian patients and compared these to the general population. METHODS: We conducted a multicentre, retrospective cohort study of PSC patients at nine tertiary liver centers across three Australian states, including two liver transplant centers. RESULTS: A total of 413 PSC patients with 3,285 person-years of follow-up were included. Three hundred and seventy-one (90%) patients had large duct PSC and 294 (71%) had associated inflammatory bowel disease. A total of 168 (41%) patients developed cirrhosis (including 34 at the time of PSC diagnosis) after a median of 15.8 (95% CI 12.4, NA) years. The composite endpoint of death or liver transplantation occurred in 49 (12%) and 78 (19%) patients, respectively, with a median transplant-free survival of 13.4 (95% CI 12.2-15) years. Compared to the general population, PSC accounted for a 240-fold increased risk of development of cholangiocarcinoma (CCA) and CCA-related death. CCA risk was increased with older age of PSC diagnosis, presence of dominant stricture and colectomy. Compared to same-aged counterparts in the general population, PSC patients who were diagnosed at an older age or with longer disease duration had reduced relative survival. CONCLUSION: In this large retrospective cohort study of PSC patients in Australia, increased age and time from diagnosis was associated with increased mortality and morbidity particularly from CCA and development of cirrhosis, necessitating need for liver transplant.

Coaxial laser absorption and optical emission spectroscopy of high-pressure aluminum monoxide.

This work advances laser absorption spectroscopy with measurements of aluminum monoxide (AlO) temperature and column density in extreme pressure (P > 60 bar) and temperature (T > 4000 K) environments. Measurements of the AlO A2Πi-X2Σ+ transition are made using a microelectromechanical system, tunable vertical cavity surface emitting laser (MEMS-VCSEL). Simultaneous emission measurements of the AlO B2Σ+-X2Σ+ transition are made along a line of sight that is coaxial with the laser absorption. Absorption temperature fits agree with emission spectra for a T = 3200 K, P = 9 bar case. In cases with T > 4000 K, P > 60 bar, absorption fits match the ambient temperature while emission fits over-estimate it, owing to high optical depths. These data juxtapose passive and active spectroscopic methods and demonstrate the versatility of AlO laser absorption in high-pressure and high-temperature environments where experimental data remain scarce, and engineering models will benefit from refined measurements.

A qualitative exploration of the feasibility and acceptability of Meaning-Centered Psychotherapy for Cancer Caregivers.

OBJECTIVE: Caregivers of patients with cancer are at significant risk for existential distress. Such distress negatively impacts caregivers' quality of life and capacity to serve in their role as healthcare proxies, and ultimately, contributes to poor bereavement outcomes. Our team developed Meaning-Centered Psychotherapy for Cancer Caregivers (MCP-C), the first targeted psychosocial intervention that directly addresses existential distress in caregivers. METHOD: Nine caregivers of patients with glioblastoma multiforme (GBM) enrolled in a pilot randomized controlled trial evaluating the feasibility, acceptability, and effects of MCP-C, and completed in-depth interviews about their experience in the therapy. One focus group with three MCP-C interventionists was also completed. RESULTS: Four key themes emerged from interviews: (1) MCP-C validated caregivers' experience of caregiving; (2) MCP-C helped participants reframe their "caregiving identity" as a facet of their larger self-identity, by placing caregiving in the context of their life's journey; (3) MCP-C enabled caregivers to find ways to assert their agency through caregiving; and (4) the structure and sequence of sessions made MCP-C accessible and feasible. Feedback from interventionists highlighted several potential manual changes and overall ways in which MCP-C can help facilitate caregivers' openness to discussing death and engaging in advanced care planning discussions with the patient. SIGNIFICANCE OF RESULTS: The overarching goal of MCP-C is to allow caregivers to concurrently experience meaning and suffering; the intervention does not seek to deny the reality of challenges endured by caregivers, but instead to foster a connection to meaning and purpose alongside their suffering. Through in-depth interviews with caregivers and a focus group with MCP interventionists, we have refined and improved our MCP-C manual so that it can most effectively assist caregivers in experiencing meaning and purpose, despite inevitable suffering.

Large Shape Staggering in Neutron-Deficient Bi Isotopes.

The changes in the mean-square charge radius (relative to ^{209}Bi), magnetic dipole, and electric quadrupole moments of ^{187,188,189,191}Bi were measured using the in-source resonance-ionization spectroscopy technique at ISOLDE (CERN). A large staggering in radii was found in ^{187,188,189}Bi^{g}, manifested by a sharp radius increase for the ground state of ^{188}Bi relative to the neighboring ^{187,189}Bi^{g}. A large isomer shift was also observed for ^{188}Bi^{m}. Both effects happen at the same neutron number, N=105, where the shape staggering and a similar isomer shift were observed in the mercury isotopes. Experimental results are reproduced by mean-field calculations where the ground or isomeric states were identified by the blocked quasiparticle configuration compatible with the observed spin, parity, and magnetic moment.

Laser Spectroscopy of Neutron-Rich

The mean-square charge radii of ^{207,208}Hg (Z=80, N=127, 128) have been studied for the first time and those of ^{202,203,206}Hg (N=122, 123, 126) remeasured by the application of in-source resonance-ionization laser spectroscopy at ISOLDE (CERN). The characteristic kink in the charge radii at the N=126 neutron shell closure has been revealed, providing the first information on its behavior below the Z=82 proton shell closure. A theoretical analysis has been performed within relativistic Hartree-Bogoliubov and nonrelativistic Hartree-Fock-Bogoliubov approaches, considering both the new mercury results and existing lead data. Contrary to previous interpretations, it is demonstrated that both the kink at N=126 and the odd-even staggering (OES) in its vicinity can be described predominately at the mean-field level and that pairing does not need to play a crucial role in their origin. A new OES mechanism is suggested, related to the staggering in the occupation of the different neutron orbitals in odd- and even-A nuclei, facilitated by particle-vibration coupling for odd-A nuclei.

Auroral ionospheric plasma flow extraction using subsonic retarding potential analyzers.

Thermal ion retarding potential analyzers (RPAs) are used to measure in situ auroral ionospheric plasma parameters. This article analyzes data from a low-resource RPA in order to quantify the capability of the sensor. The RPA collects a sigmoidal current-voltage (I-V) curve, which depends on a non-linear combination of Maxwellian plasma parameters, so a forward-modeling procedure is used to match the best choice plasma parameters for each I-V curve. First, the procedure is used, given constraining information about the flow moment, to find scalar plasma parameters-ion temperature, ion density, and spacecraft sheath potential-for a single I-V curve interpreted in the context of a Maxwellian plasma distribution. Second, two azimuthally separated I-V curves from a single sensor on the spinning spacecraft are matched, given constraining information on density and sheath potential, to determine the bulk plasma flow components. These flows are compared to a high-fidelity, high-resource flow diagnostic. In both cases, the procedure's sensitivity to variations in constraining diagnostics is tested to ensure that the matching procedure is robust. Finally, a standalone analysis is shown, providing plasma scalar and flow parameters using known payload velocity and International Reference Ionosphere density as input information. The results show that the sensor can determine scalar plasma measurements as designed, as well as determine plasma DC flows to within hundreds of m/s error compared to a high-fidelity metric, thus showing their capability to replace higher-resource methods for determining DC plasma flows when coarse-resolution measurements at in situ spatial scales are suitable.

Mars Extant Life: What's Next? Conference Report.

On November 5-8, 2019, the "Mars Extant Life: What's Next?" conference was convened in Carlsbad, New Mexico. The conference gathered a community of actively publishing experts in disciplines related to habitability and astrobiology. Primary conclusions are as follows: A significant subset of conference attendees concluded that there is a realistic possibility that Mars hosts indigenous microbial life. A powerful theme that permeated the conference is that the key to the search for martian extant life lies in identifying and exploring refugia ("oases"), where conditions are either permanently or episodically significantly more hospitable than average. Based on our existing knowledge of Mars, conference participants highlighted four potential martian refugium (not listed in priority order): Caves, Deep Subsurface, Ices, and Salts. The conference group did not attempt to reach a consensus prioritization of these candidate environments, but instead felt that a defensible prioritization would require a future competitive process. Within the context of these candidate environments, we identified a variety of geological search strategies that could narrow the search space. Additionally, we summarized a number of measurement techniques that could be used to detect evidence of extant life (if present). Again, it was not within the scope of the conference to prioritize these measurement techniques-that is best left for the competitive process. We specifically note that the number and sensitivity of detection methods that could be implemented if samples were returned to Earth greatly exceed the methodologies that could be used at Mars. Finally, important lessons to guide extant life search processes can be derived both from experiments carried out in terrestrial laboratories and analog field sites and from theoretical modeling.

CyBorD-DARA is potent initial induction for MM and enhances ADCP: initial results of the 16-BCNI-001/CTRIAL-IE 16-02 study.

Daratumumab (DARA) has shown impressive activity in combination with other agents for the treatment of multiple myeloma (MM). We conducted a phase 1b study to assess the safety and preliminary efficacy, as well as potential mechanisms of action, of DARA (16 mg/kg) in combination with a weekly schedule of subcutaneous bortezomib (1.3-1.5 mg/m2), cyclophosphamide (150-300 mg/m2), and dexamethasone (40 mg) (CyBorD DARA) as initial induction before autologous stem cell transplantation (ASCT). Eligible patients were ≤70 years of age with untreated MM requiring treatment and who lacked significant comorbidities. A total of 18 patients were enrolled. Their median age was 56 years (range, 32-66 years), and all patients had Eastern Cooperative Oncology Group performance status ≤1. The International Staging System stages were I, II, and III in 78%, 17%, and 6% of patients, respectively; 28% of patients had high-risk genetic features. There was no dose-limiting toxicity, and the incidence of grade 3 or 4 infection or neutropenia was <10%. On an intention-to-treat basis, 94% achieved ≥very good partial response with ≥complete response in 44% of patients. Among 14 of 15 patients who underwent ASCT and were evaluable for response, all 14 achieved at least very good partial response, with 8 (57%) of 14 achieving complete response. After ASCT, 10 (83%) of 12 patients in whom minimal residual disease analysis was possible were negative at a sensitivity of 10-5 (56% on intention-to-treat/whole study population) according to next-generation sequencing. Flow cytometry analysis of patient samples indicated CyBorD DARA induced activation of macrophage-mediated antibody-dependent cellular phagocytosis. This trial was registered at www.clinicaltrials.gov as #NCT02955810.

Development of alcohol treatment for UK military personnel.

The consumption of alcohol in the UK Armed Forces (AF) as 'an agent to assist cohesion and informal operational debriefing' is a social and psychological conceptualisation that has some empirical support. Indisputable data exist to suggest that high levels of alcohol misuse and related problems are prevalent among UK AF. Recent research indicates that the overall level of hazardous alcohol consumption remains high in the UK military, with little evidence of reduced consumption over time. Meanwhile, risky drinking in the general population appears to be decreasing. This paper describes work to develop a key aspect of an integrated care pathway for UK military personnel at all levels of alcohol risk. The project focuses on the development of an evidence-based treatment response across primary care and mental health services that will link with preventative initiatives. Specialist (ie, substance misuse) input from the Defence Clinical Psychology Service across and within Departments of Community Mental Health lends an overarching perspective to a major healthcare and organisational concern for the UK AF. Work towards a consistent treatment pathway for alcohol misuse is also benefiting from collaboration between the Ministry of Defence and Public Health England.

Lack of proton pump inhibitor trial prior to commencing therapy for eosinophilic esophagitis is common in the community.

Eosinophilic esophagitis is characterized by eosinophil inflammation restricted to the esophagus and the resulting symptoms of esophageal dysfunction. Critical to the diagnosis of eosinophilic esophagitis is a trial of proton pump inhibitor therapy to exclude alternative causes of esophageal eosinophilia such as proton pump inhibitor-responsive esophageal eosinophilia. While consensus guidelines recommend a proton pump inhibitor trial prior to diagnosis, little is known about its implementation in clinical practice. The primary aim of this study is to assess the frequency of proton pump inhibitor trial prior to the diagnosis of eosinophilic esophagitis in community practice. The secondary aim is to assess the frequency of other treatments for eosinophilic esophagitis, including topical steroids and/or dietary therapy, in patients who did not undergo a proton pump inhibitor trial prior to diagnosis or who had an alternative diagnosis to eosinophilic esophagitis upon completed workup. We conducted a single-center, case series of patients referred to the Hospital of the University of Pennsylvania for eosinophilic esophagitis management between 2010 and 2015. This case series consisted of 125 patients who were referred from community practitioners with a presumptive diagnosis of eosinophilic esophagitis. Upon review, 90 out of 125 (72%) patients had not had a proton pump inhibitor trial or esophageal pH testing prior to the diagnosis of eosinophilic esophagitis being made. Of these patients, 77.8% (70/90) had already received either topical steroid or dietary therapy for presumed eosinophilic esophagitis. Of the 125 patients initially diagnosed with eosinophilic esophagitis, 32 (25.6%) were found to have an alternative diagnosis, and 79.2% of this subset of patients (25/32) had previously received topical steroid or dietary therapy. This study demonstrates that a substantial number of patients with presumed eosinophilic esophagitis have not had a proton pump inhibitor trial prior to diagnosis in community practice. This led to the misclassification of patients and potentially to the use of less optimal medical therapies in a substantial number of these patients.

TV viewing time is associated with increased all-cause mortality in Brazilian adults independent of physical activity.

The purpose of this study was to investigate the association between television (TV) viewing and all-cause mortality among Brazilian adults after 6 years of follow-up. This longitudinal study started in 2010 in the city of Bauru, SP, Brazil, and involved 970 adults aged ≥50 years. Mortality was reported by relatives and confirmed in medical records of the Brazilian National Health System. Physical activity (PA) and TV viewing were assessed by the Baecke questionnaire. Health status, sociodemographic and behavioral covariates were considered as potential confounders. After 6 years of follow-up, 89 deaths were registered (9.2% [95% CI=7.4%-11%]). Type 2 diabetes mellitus was associated with higher risk of mortality (P-value=.012). Deaths correlated significantly with age (ρ=.188; P-value=.001), overall PA score (ρ=-.128; P-value=.001) and TV viewing (ρ=.086; P-value=.007). Lower percentage of participants reported TV viewing time as often (16%) and very often (5.7%), but there was an association between higher TV viewing time ("often" and "very often" grouped together) and increased mortality after 6 years of follow-up (P-value=.006). The higher TV viewing time was associated with a 44.7% increase in all-cause mortality (HR=1.447 [1.019-2.055]), independently of other potential confounders. In conclusion, the findings from this cohort study identified increased risk of mortality among adults with higher TV viewing time, independently of PA and other variables.

A small spacecraft for multipoint measurement of ionospheric plasma.

Measurement of ionospheric plasma is often performed by a single in situ device or remotely using cameras and radar. This article describes a small, low-resource, deployed spacecraft used as part of a local, multipoint measurement network. A B-field aligned sounding rocket ejects four of these spin-stabilized spacecraft in a cross pattern. In this application, each spacecraft carries two retarding potential analyzers which are used to determine plasma density, flow, and ion temperature. An inertial measurement unit and a light-emitting diode array are used to determine the position and orientation of the devices after deployment. The design of this spacecraft is first described, and then results from a recent test flight are discussed. This flight demonstrated the successful operation of the deployment mechanism and telemetry systems, provided some preliminary plasma measurements in a simple mid-latitude environment, and revealed several design issues.

Evaluation of Temporal Changes in Urine-based Metabolomic and Kidney Injury Markers to Detect Compound Induced Acute Kidney Tubular Toxicity in Beagle Dogs.

Urinary protein biomarkers and metabolomic markers have been leveraged to detect acute Drug Induced Kidney Injury (DIKI) in rats; however, the utility of these indicators to enable early detection of DIKI in canine models has not been well documented. Therefore, we evaluated temporal changes in biomarkers and metabolites in urine from male and female beagle dogs. Gentamicin- induced kidney lesions in male dogs were characterized by moderate to severe tubular epithelial cell degeneration/necrosis, epithelial cell regeneration and dilation; and a unique urinebased metabolomic fingerprint. These metabolite changes included time and treatment-dependent increases in lactate, taurine, glucose, lactate, alanine, and citrate as well as 9 other known metabolites. As early as 3 days post dose, gentamicin induced increases in urinary albumin, clusterin, neutrophil gelatinase associated protein (NGAL) and total protein concentrations. Urinary albumin, clusterin, and NGAL showed earlier and more robust elevations than traditional kidney safety biomarkers, blood urea nitrogen and serum creatinine. Elevations in urinary kidney injury molecule 1 (KIM-1) were less reliable for detection of gentamicin nephrotoxicity in dogs based on values generated utilizing multiple first-generation, canine-specific KIM-1 immunoassays. The metabolic fingerprint was further evaluated in male and female dogs that received Compound A which induced slightly reversible renal tubular alterations characterized as degeneration/necrosis and concurrent significant increases in urinary taurine amongst other markers. These data support further investigations to demonstrate the value of urinary metabolites, albumin, clusterin, NGAL and taurine as promising markers to enable early detection of DIKI in dogs.

Esophageal distensibility measurement: impact on clinical management and procedure length.

Luminal distensibility measurement has demonstrated relevance to various disease processes, though its effects on clinical decision-making have been less well understood. This study aims to characterize the clinical impact of impedance planimetry measurement as well as the learning curve associated with its use in the esophagus. A single provider performed distensibility measurement in conjunction with upper endoscopy for a variety of clinical indications with the functional lumen imaging probe (FLIP) over a period of 21 months. Procedural data were prospectively collected and, along with medical records, retrospectively reviewed. Seventy-three procedures (70 patients) underwent esophageal distensibility measurement over the timeline of this study. The most common procedural indications were known or suspected achalasia (32.9%), dysphagia with connective tissue disease (13.7%), eosinophilic esophagitis (12.3%), and dysphagia with prior fundoplication (9.6%). FLIP results independently led to a change in management in 29 (39.7%) cases and supported a change in management in an additional 15 (20.5%) cases. The most common change in management was a new or amended therapeutic procedure (79.5%). Procedural time added by distensibility measurement was greater among earlier cases than among later cases. The median time added overall was 5 minutes and 46 seconds. Procedural time added varied significantly by procedural indication, but changes in management did not. Distensibility measurement added meaningful diagnostic information that impacted therapeutic decision-making in the majority of cases in which it was performed. Procedural time added by this modality is typically modest and decreases with experience.