Development of tumor-reactive T cells after nonmyeloablative allogeneic hematopoietic stem cell transplant for chronic lymphocytic leukemia.

PURPOSE: Allogeneic nonmyeloablative hematopoietic stem cell transplant (NM-HSCT) can result in durable remission of chronic lymphocytic leukemia (CLL). It is thought that the efficacy of NM-HSCT is mediated by recognition of tumor cells by T cells in the donor stem cell graft. We evaluated the development of CTLs specific for CLL after NM-HSCT to determine if their presence correlated with antitumor efficacy. EXPERIMENTAL DESIGN: Peripheral blood mononuclear cells obtained from 12 transplant recipients at intervals after NM-HSCT were stimulated in vitro with CLL cells. Polyclonal T-cell lines and CD8(+) T-cell clones were derived from these cultures and evaluated for lysis of donor and recipient target cells including CLL. The presence and specificity of responses was correlated with clinical outcomes. RESULTS: Eight of the 12 patients achieved remission or a major antitumor response and all 8 developed CD8(+) and CD4(+) T cells specific for antigens expressed by CLL. A clonal analysis of the CD8(+) T-cell response identified T cells specific for multiple minor histocompatibility (H) antigens expressed on CLL in six of the responding patients. A significant fraction of the CD8(+) T-cell response in some patients was also directed against nonshared tumor-specific antigens. By contrast, CLL-reactive T cells were not detected in the four patients who had persistent CLL after NM-HSCT, despite the development of graft-versus-host disease. CONCLUSIONS: The development of a diverse T-cell response specific for minor H and tumor-associated antigens expressed by CLL predicts an effective graft-versus-leukemia response after NM-HSCT

MyChart Messaging: Patient Preferences about Timing of Provider Responses to Medical Advice Requests

Background: Patients frequently utilize portal messaging to reach their healthcare provider.1 This mode of communication allows for greater patient engagement in health concerns.2 MyChart messaging has grown recently, increasing physician workload.3,4 Understanding patient preferences for MyChart messaging may improve patient communication, potentially decreasing the response burden on physicians. Methods: A 12-question REDCap survey was sent via MyChart message to 31,502 patients in 8 UVM Health Network (UVMHN) affiliated adult primary care and family medicine practices. Survey data were analyzed in excel. Key Results: The survey was completed by 2011 (6.4%) patients, with 77% of respondents having used MyChart to ask their provider a question. MyChart messaging is always or often (69.1%) the first method patients use to contact their healthcare provider with 22% submitting urgent concerns. There is a significant association between when a patient prefers to receive a message and the time it takes providers to respond to their message (p \u3c 0.001). On average, patients would prefer to not restrict MyChart messaging to business hours. Discussion: Patients prefer prompt message responses from their providers and providers are meeting this preference. Future work could better observe the relationship between provider response time and patient preferences for physician response time. Data from Epic should be analyzed to determine if patient perceptions align with MyChart message records. Other efforts should include educating patients about appropriate messages to send via MyChart, or if a phone call is warranted. 1 North F, Luhman KE, Mallmann EA, Mallmann TJ, Tulledge-Scheitel SM, North EJ, Pecina JL. A Retrospective Analysis of Provider-to-Patient Secure Messages: How Much Are They Increasing, Who Is Doing the Work, and Is the Work Happening After Hours? JMIR Med Inform. 2020 Jul 8;8(7):e16521. doi: 10.2196/16521. 2 Avdagovska M, Ballermann M, Olson K, Graham T, Menon D, Stafinski T. Patient Portal Implementation and Uptake: Qualitative Comparative Case Study. J Med Internet Res. 2020;22(7):e18973. 3 Arndt BG, Beasley JW, Watkinson MD, et al. Tethered to the EHR: Primary Care Physician Workload Assessment Using EHR Event Log Data and Time-Motion Observations. Ann Fam Med. 2017;15(5):419-426. 4 Laccetti AL, Chen B, Cai J, et al. Increase in Cancer Center Staff Effort Related to Electronic Patient Portal Use. J Oncol Pract. 2016 (12):e981- e990

Provider Perspectives on Language Barriers in MyChart Enrollment for Patients with Limited English Proficiency

Background: There are 25 million people in the United States with limited English proficiency (LEP). Patients with LEP are a vulnerable population who may have worse health outcomes compared to English-proficient patients, as they face barriers to safe, effective, and high-quality care. Previous studies show this population is likely to benefit from utilization of patient portals, which allow users to access personal health information and communicate with healthcare providers. Current literature reports that patients with LEP and their families have a strong interest in using the patient portal as it can help them understand their providers and health, remember their care plan, and have more control over their health. However, there is less portal access and utilization among patients with LEP. This study was conducted to obtain provider perspectives surrounding MyChart engagement of patients with LEP to identify potential barriers to MyChart enrollment at the University of Vermont Health Network (UVMHN). Methods: EPIC’s Slicer Dicer tool was utilized to obtain UVMHN patient counts organized by reported language and MyChart activation. Data was collected from an anonymous REDCap survey sent to 211 providers within UVMHN Departments of General Internal Medicine, Family Medicine, and Pediatrics, and analyzed utilizing Excel. Results: 67.9% of UVMHN Primary Care English speakers have MyChart activated compared to 46.9% of patients with LEP. Providers strongly believe that MyChart is beneficial to patients and families with 72.1% of providers agreeing that it improves the patient-provider relationship. When asked specifically about patients with LEP, 36% of providers agree that MyChart access is beneficial to care. 49% report they are likely to encourage MyChart enrollment to their patients with LEP; however, only 14% know how to assist in enrollment. Differences in knowledge of language services are seen in different visit modalities: 78.1% of providers report ability to provide language services during in-person visits compared to 48.8% for video visits and 46.3% for telephone visits. Once made aware of the differences in MyChart activation status between English proficient patients and patients with LEP, providers frequently requested more education around language assistance, MyChart activation instructions to provide patients in their dominant language, translation tools within EPIC, and training for support staff to also encourage patients with LEP to enroll in MyChart. Conclusions: While providers overwhelmingly believe MyChart is useful to patient care and are likely to recommend it to their patients with LEP, they lack the tools and education necessary to aid in equitable enrollment. Educational materials and translated resources should be created for providers to utilize in assisting their patients with LEP. A follow-up study with patients would provide an opportunity to compare patient and provider responses and gain additional perspectives on MyChart access and utilization

Submillimeter Number Counts From Statistical Analysis of BLAST Maps

We describe the application of a statistical method to estimate submillimeter galaxy number counts from confusion limited observations by the Balloon-borne Large Aperture Submillimeter Telescope (BLAST). Our method is based on a maximum likelihood fit to the pixel histogram, sometimes called 'P(D)', an approach which has been used before to probe faint counts, the difference being that here we advocate its use even for sources with relatively high signal-to-noise ratios. This method has an advantage over standard techniques of source extraction in providing an unbiased estimate of the counts from the bright end down to flux densities well below the confusion limit. We specifically analyse BLAST observations of a roughly 10 sq. deg. map centered on the Great Observatories Origins Deep Survey South (GOODS-S) field. We provide estimates of number counts at the three BLAST wavelengths, 250, 350, and 500 microns; instead of counting sources in flux bins we estimate the counts at several flux density nodes connected with power-laws. We observe a generally very steep slope for the counts of about -3.7 at 250 microns and -4.5 at 350 and 500 microns, over the range ~0.02-0.5 Jy, breaking to a shallower slope below about 0.015 Jy at all three wavelengths. We also describe how to estimate the uncertainties and correlations in this method so that the results can be used for model-fitting. This method should be well-suited for analysis of data from the Herschel satellite.Comment: Accepted for publication in the Astrophysical Journal; see associated data and other papers at http://blastexperiment.info

Using a personalized DVD to prescribe an exercise program to older people post-hip fracture enhances adherence to the exercises: A feasibility study

Optimum recovery from hip fracture has been linked to the provision of effective rehabilitation, but levels of adherence vary among older patients. In this feasibility study a novel personalized DVD was designed for four participants, which delivered a 5 week tailored home exercise program (HEP), with the participant being videoed completing their exercises. Treatment fidelity of the DVD HEP was evaluated, including participants' perceptions of and response to the DVD-HEP, which was explored using diaries and interviews and analyzed thematically. Secondary outcome measures including exercise adherence and self-efficacy for exercise were analyzed using descriptive statistics. Levels of adherence to the HEP were 1.2-3.5 times more than the minimum prescribed dose and participants demonstrated higher levels of self-efficacy for exercise. Adherence was found to be enhanced by physical improvement, positive self-reflection about engagement in the DVD-HEP, the format of the DVD, and increased self-efficacy. Personalized DVDs may be a feasible method of promoting adherence to home exercise programs among older patients

Mechanism of Sphingosine 1-Phosphate- and Lysophosphatidic Acid-Induced Up-Regulation of Adhesion Molecules and Eosinophil Chemoattractant in Nerve Cells

The lysophospholipids sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA) act via G-protein coupled receptors S1P1–5 and LPA1–3 respectively, and are implicated in allergy. Eosinophils accumulate at innervating cholinergic nerves in asthma and adhere to nerve cells via intercellular adhesion molecule-1 (ICAM-1). IMR-32 neuroblastoma cells were used as an in vitro cholinergic nerve cell model. The Gi coupled receptors S1P1, S1P3, LPA1, LPA2 and LPA3 were expressed on IMR-32 cells. Both S1P and LPA induced ERK phosphorylation and ERK- and Gi-dependent up-regulation of ICAM-1 expression, with differing time courses. LPA also induced ERK- and Gi-dependent up-regulation of the eosinophil chemoattractant, CCL-26. The eosinophil granule protein eosinophil peroxidase (EPO) induced ERK-dependent up-regulation of transcription of S1P1, LPA1, LPA2 and LPA3, providing the situation whereby eosinophil granule proteins may enhance S1P- and/or LPA- induced eosinophil accumulation at nerve cells in allergic conditions

Student Recital (May 1, 2013)

Etude No. 1 / Everett “Vic” Firth Dan Maloney, snare drum French Suite No. 2, BWV 813 / Johann Sebastian Bach Air David Smith, piano Night and Day / Cole Porter What is This Thing Called Love / C. Porter Colin Sullivan, baritone Left Behind / Duncan Sheik Jack Cappadona, tenor Yesterday’s / Otto Harbach Fools Rush In (Where Angels Fear to Tread) / Johnny Mercer Danni Vitorino, tenor You Walk With Me / David Yazbeck Jack Cappadona, tenor Danni Vitorino, tenor Ulrica’s Aria from un ballo in Maschera / Guiseppe Verdi Va! Laisse couler mes larmes / Jules Massenet Diane Card, alto Sonata No, 4 in C Major, BWV 1033 / J. S. Bach Andante Allegro Marie Doyon, flute Three Songs of the Sea, Op. 1 / Roger Quilter The Sea-Bird Moonlight By The Sea Thomas Manning, baritone The Ballad of Baby Doe / Douglas Moore Willow Song Jordan Ennis, soprano Adieu Notre Petite Table / J. Massenet Ach ich fuhl’s from Die Zauberflote, K. 620 / Wolfgang Amadeus Mozart Mary Sanker, soprano Se tu m’ami (If You Love Me) / Alessandro Parisotti I Attempt From Love’s Sickness / Henry Purcell Justine Smigel, soprano Ave Maria / Franz Schubert A Quiet Girl / Leonard Bernstein Michael Bradley, baritone The Point of No Return / Andrew Lloyd Weber Michael Bradley, baritone Stephanie Blood, soprano My Lovely Celia / George Monro I Have Dreamed from The King and I / Richard Rogers Richard Moran, tenor Adelita / Francisco Tarrega Cancion Del Emperador / Luis De Navaex Bryan Picher, guitar Cello Suite No. 1, BWV 1007 / J. S. Bach Prelude Mark Gavin, guitarhttps://vc.bridgew.edu/student_concerts/1042/thumbnail.jp

Temporal changes in total and size-fractioned chlorophyll-a in surface waters of three provinces in the Atlantic Ocean (September to November) between 2003 and 2010

Phytoplankton total chlorophyll concentration (TCHLa) and phytoplankton size structure are two important ecological indicators in biological oceanography. Using high performance liquid chromatography (HPLC) pigment data, collected from surface waters along the Atlantic Meridional Transect (AMT), we examine temporal changes in TCHLa and phytoplankton size class (PSC: micro-, nano- and pico-phytoplankton) between 2003 and 2010 (September to November cruises only), in three ecological provinces of the Atlantic Ocean. The HPLC data indicate no significant change in TCHLa in northern and equatorial provinces, and an increase in the southern province. These changes were not significantly different to changes in TCHLa derived using satellite ocean-colour data over the same study period. Despite no change in AMT TCHLa in northern and equatorial provinces, significant differences in PSC were observed, related to changes in key diagnostic pigments (fucoxanthin, peridinin, 19’-hexanoyloxyfucoxanthin and zeaxanthin), with an increase in small cells (nano- and pico-phytoplankton) and a decrease in larger cells (micro-phytoplankton). When fitting a three-component model of phytoplankton size structure ̶ designed to quantify the relationship between PSC and TCHLa ̶ to each AMT cruise, model parameters varied over the study period. Changes in the relationship between PSC and TCHLa have wide implications in ecology and marine biogeochemistry, and provide key information for the development and use of empirical ocean-colour algorithms. Results illustrate the importance of maintaining a time-series of in-situ observations in remote regions of the ocean, such as that acquired in the AMT programme