Student Recital (April 30, 2015)

Concerto for Flute and Piano, Op. 107 / Cecile Chamanade Moderato Marie Doyon, flute Morceau Symphonique, Op. 88 / Alexandre Guilmant Sarah Emanuel, trombone Lute Suite in Eb Major, BWV 998 / Johann Sebastian Bach Prelude Killian Kerrigan, guitar Concertante / Harold L Walters Maestoso Piu animato Joselyn Morritt, tuba Fantasie No. 7 en Mi minore / Francesca da Milano Sean Donovan, guitar Violin Partita No. 2 in D minor, BWV 1004 / J. S. Bach Allemanda Gail Colombo, violin Gott Im Frühling, D. 448 / Franz Schubert Lullaby from The Consul / Gian Carlo Menotti Justine Smigel, soprano Homenaje, G. 56 / Manuel de Falla Sonata en Sol Majeur, K. 391 / Domenico Scarlatti Allegro Thomas Prosser, guitar Sonata in C Major, Hob XVI / Franz Joseph Haydn Allegro Deux Arabesque, L. 61 / Claude Debussy Andantino con moto Alexander Heinrich, piano Pur dicesti, o bocca bella / Antonio Lotti Brooke Spiegel, soprano Sonata No. 11 (St. Marc) / Tommaso Giovanni Albinoni Grave Allegro Joanna Richards, trumpet Variation on a theme by Robert Schumann, Op. 20 / Clara Schumann Theme Variation I Variation II Variation III Jiaying Zhu, pianohttps://vc.bridgew.edu/student_concerts/1091/thumbnail.jp

Ten-year mortality, disease progression, and treatment-related side effects in men with localised prostate cancer from the ProtecT randomised controlled trial according to treatment received

Background The ProtecT trial reported intention-to-treat analysis of men with localised prostate cancer randomly allocated to active monitoring (AM), radical prostatectomy, and external beam radiotherapy. Objective To report outcomes according to treatment received in men in randomised and treatment choice cohorts. Design, setting, and participants This study focuses on secondary care. Men with clinically localised prostate cancer at one of nine UK centres were invited to participate in the treatment trial comparing AM, radical prostatectomy, and radiotherapy. Intervention Two cohorts included 1643 men who agreed to be randomised and 997 who declined randomisation and chose treatment. Outcome measurements and statistical analysis Analysis was carried out to assess mortality, metastasis and progression and health-related quality of life impacts on urinary, bowel, and sexual function using patient-reported outcome measures. Analysis was based on comparisons between groups defined by treatment received for both randomised and treatment choice cohorts in turn, with pooled estimates of intervention effect obtained using meta-analysis. Differences were estimated with adjustment for known prognostic factors using propensity scores. Results and limitations According to treatment received, more men receiving AM died of PCa (AM 1.85%, surgery 0.67%, radiotherapy 0.73%), whilst this difference remained consistent with chance in the randomised cohort (p = 0.08); stronger evidence was found in the exploratory analyses (randomised plus choice cohort) when AM was compared with the combined radical treatment group (p = 0.003). There was also strong evidence that metastasis (AM 5.6%, surgery 2.4%, radiotherapy 2.7%) and disease progression (AM 20.35%, surgery 5.87%, radiotherapy 6.62%) were more common in the AM group. Compared with AM, there were higher risks of sexual dysfunction (95% at 6 mo) and urinary incontinence (55% at 6 mo) after surgery, and of sexual dysfunction (88% at 6 mo) and bowel dysfunction (5% at 6 mo) after radiotherapy. The key limitations are the potential for bias when comparing groups defined by treatment received and changes in the protocol for AM during the lengthy follow-up required in trials of screen-detected PCa. Conclusions Analyses according to treatment received showed increased rates of disease-related events and lower rates of patient-reported harms in men managed by AM compared with men managed by radical treatment, and stronger evidence of greater PCa mortality in the AM group. Patient summary More than 95 out of every 100 men with low or intermediate risk localised prostate cancer do not die of prostate cancer within 10 yr, irrespective of whether treatment is by means of monitoring, surgery, or radiotherapy. Side effects on sexual and bladder function are better after active monitoring, but the risks of spreading of prostate cancer are more common

Functional and quality of life outcomes of localised prostate cancer treatments (prostate testing for cancer and treatment [ProtecT] study)

Objective To investigate the functional and quality of life (QoL) outcomes of treatments for localised prostate cancer and inform treatment decision-making. Patients and Methods Men aged 50–69 years diagnosed with localised prostate cancer by prostate-specific antigen testing and biopsies at nine UK centres in the Prostate Testing for Cancer and Treatment (ProtecT) trial were randomised to, or chose one of, three treatments. Of 2565 participants, 1135 men received active monitoring (AM), 750 a radical prostatectomy (RP), 603 external-beam radiotherapy (EBRT) with concurrent androgen-deprivation therapy (ADT) and 77 low-dose-rate brachytherapy (BT, not a randomised treatment). Patient-reported outcome measures (PROMs) completed annually for 6 years were analysed by initial treatment and censored for subsequent treatments. Mixed effects models were adjusted for baseline characteristics using propensity scores. Results Treatment-received analyses revealed different impacts of treatments over 6 years. Men remaining on AM experienced gradual declines in sexual and urinary function with age (e.g., increases in erectile dysfunction from 35% of men at baseline to 53% at 6 years and nocturia similarly from 20% to 38%). Radical treatment impacts were immediate and continued over 6 years. After RP, 95% of men reported erectile dysfunction persisting for 85% at 6 years, and after EBRT this was reported by 69% and 74%, respectively (P < 0.001 compared with AM). After RP, 36% of men reported urinary leakage requiring at least 1 pad/day, persisting for 20% at 6 years, compared with no change in men receiving EBRT or AM (P < 0.001). Worse bowel function and bother (e.g., bloody stools 6% at 6 years and faecal incontinence 10%) was experienced by men after EBRT than after RP or AM (P < 0.001) with lesser effects after BT. No treatment affected mental or physical QoL. Conclusion Treatment decision-making for localised prostate cancer can be informed by these 6-year functional and QoL outcomes

Single‐cell oxygen saturation imaging shows that gas exchange by red blood cells is not impaired in COVID‐19 patients

SARS‐CoV‐2 coronavirus infection is characterised by a marked inflammatory state and viral pneumonitis. A striking clinical feature is severe hypoxaemia, often in the presence of near‐normal lung mechanics

Fibroblast growth factor-23 and risk of cardiovascular diseases: a Mendelian randomization study

Background: Fibroblast growth factor 23 (FGF-23) is associated with a range of cardiovascular and non-cardiovascular diseases in conventional epidemiological studies, but substantial residual confounding may exist. Mendelian randomization approaches can help control for such confounding. Methods: SCALLOP consortium data on 19,195 participants were used to generate an FGF-23 genetic score. Data from 337,448 UK Biobank participants were used to estimate associations between higher genetically-predicted FGF-23 concentration and the odds of any atherosclerotic cardiovascular disease (n=26,266 events), of any non-atherosclerotic cardiovascular disease (n=12,652), and of non-cardiovascular diseases previously linked to FGF-23. Measurements of carotid intima-media thickness and left ventricular mass were available in a subset. Associations with cardiovascular outcomes were also tested in three large case-control consortia: CARDIOGRAMplusC4D (coronary artery disease, n=181,249 cases), MEGASTROKE (stroke, n=34,217), and HERMES (heart failure, n=47,309). Results: We identified 34 independent variants for circulating FGF-23 which formed a validated genetic score. There were no associations between genetically-predicted FGF-23 and any of the cardiovascular or non-cardiovascular outcomes. In UK Biobank, the odds ratio for any atherosclerotic cardiovascular disease per 1-SD higher genetically-predicted logFGF-23 was 1.03 (95% confidence interval [CI] 0.98-1.08), and for any non-atherosclerotic cardiovascular disease was 1.01 (0.94-1.09). The odds ratios in the case-control consortia were 1.00 (0.97-1.03) for coronary artery disease, 1.01 (0.95-1.07) for stroke, and 1.00 (0.95-1.05) for heart failure. In those with imaging, logFGF-23 was not associated with carotid or cardiac abnormalties. Conclusion: Genetically predicted FGF-23 levels are not associated atherosclerotic and non-atherosclerotic cardiovascular diseases, suggesting no important causal link

Guitars and Textures: A Special Spring Concert (April 5, 2016)

From Three Way Stretch / Phil Dennys 2. Clowning Around 3. Bumpy Road Dominique Moran, Ed Salate, and Zenan Sun, piano Viennese Waltz / Robert Fuchs Zenan Sun and Ed Salate, piano Sometimes I Feel Like a Motherless Child arr. Harry Burleigh Dominique Durden, soprano Zenan Sun, piano Poetry The Resistance – Dominique Durden Privilege – Christopher Melville Sunset Boulevard / Composed by Textures Ensemble Nahthan Paul and Dominique Durden, sopranos Dominique Moran, piano Christopher Melville, guitar At Last / Harry Warren Nahthan Paul, soprano Etude Op. 10, No. 1 in C Major / F. Chopin Hannah To, piano Naokolo (Around Dance) / Dusan Bogdanovic Introduction Kolo (Round Dance) Fugue Song BSU Guitar Ensemble Danza de la Seduccion from Danzas Gitanas, Op. 55 / J. Turina BSU Guitar Ensemble Movement 1 from Suite, Op. 14 / Béla Bartók BSU Guitar Ensemblehttps://vc.bridgew.edu/student_concerts/1111/thumbnail.jp

Classification of intestinal T-cell receptor repertoires using machine learning methods can identify patients with coeliac disease regardless of dietary gluten status.

In coeliac disease (CeD), immune-mediated small intestinal damage is precipitated by gluten, leading to variable symptoms and complications, occasionally including aggressive T-cell lymphoma. Diagnosis, based primarily on histopathological examination of duodenal biopsies, is confounded by poor concordance between pathologists and minimal histological abnormality if insufficient gluten is consumed. CeD pathogenesis involves both CD4+ T-cell-mediated gluten recognition and CD8+ and γδ T-cell-mediated inflammation, with a previous study demonstrating a permanent change in γδ T-cell populations in CeD. We leveraged this understanding and explored the diagnostic utility of bulk T-cell receptor (TCR) sequencing in assessing duodenal biopsies in CeD. Genomic DNA extracted from duodenal biopsies underwent sequencing for TCR-δ (TRD) (CeD, n = 11; non-CeD, n = 11) and TCR-γ (TRG) (CeD, n = 33; non-CeD, n = 21). We developed a novel machine learning-based analysis of the TCR repertoire, clustering samples by diagnosis. Leave-one-out cross-validation (LOOCV) was performed to validate the classification algorithm. Using TRD repertoire, 100% (22/22) of duodenal biopsies were correctly classified, with a LOOCV accuracy of 91%. Using TCR-γ (TRG) repertoire, 94.4% (51/54) of duodenal biopsies were correctly classified, with LOOCV of 87%. Duodenal biopsy TRG repertoire analysis permitted accurate classification of biopsies from patients with CeD following a strict gluten-free diet for at least 6 months, who would be misclassified by current tests. This result reflects permanent changes to the duodenal γδ TCR repertoire in CeD, even in the absence of gluten consumption. Our method could complement or replace histopathological diagnosis in CeD and might have particular clinical utility in the diagnostic testing of patients unable to tolerate dietary gluten, and for assessing duodenal biopsies with equivocal features. This approach is generalisable to any TCR/BCR locus and any sequencing platform, with potential to predict diagnosis or prognosis in conditions mediated or modulated by the adaptive immune response. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland

Fibroblast Growth Factor-23 and Risk of Cardiovascular Diseases A Mendelian Randomization Study

Background Fibroblast growth factor-23 (FGF-23) is associated with a range of cardiovascular and noncardiovascular diseases in conventional epidemiological studies, but substantial residual confounding may exist. Mendelian randomization approaches can help control for such confounding.Methods SCALLOP Consortium data of 19,195 participants were used to generate an FGF-23 genetic score. Data from 337,448 UK Biobank participants were used to estimate associations between higher genetically predicted FGF-23 concentration and the odds of any atherosclerotic cardiovascular disease (n=26,266 events), nonatherosclerotic cardiovascular disease (n=12,652), and noncardiovascular diseases previously linked to FGF-23. Measurements of carotid intima-media thickness and left ventricular mass were available in a subset. Associations with cardiovascular outcomes were also tested in three large case-control consortia: CARDIOGRAMplusC4D (coronary artery disease, n=181,249 cases), MEGASTROKE (stroke, n=34,217), and HERMES (heart failure, n=47,309).Results We identified 34 independent variants for circulating FGF-23, which formed a validated genetic score. There were no associations between genetically predicted FGF-23 and any of the cardiovascular or non cardiovascular outcomes. In UK Biobank, the odds ratio (OR) for any atherosclerotic cardiovascular disease per 1-SD higher genetically predicted logFGF-23 was 1.03 (95% confidence interval [95% CI], 0.98 to 1.08), and for any nonatherosclerotic cardiovascular disease, it was 1.01 (95% CI, 0.94 to 1.09). The ORs in the case-control consortia were 1.00 (95% CI, 0.97 to 1.03) for coronary artery disease, 1.01 (95% CI, 0.95 to 1.07) for stroke, and 1.00 (95% CI, 0.95 to 1.05) for heart failure. In those with imaging, logFGF-23 was not associated with carotid or cardiac abnormalities.Conclusions Genetically predicted FGF-23 levels are not associated with atherosclerotic and nonatherosclerotic cardiovascular diseases, suggesting no important causal link