Growth and differentiation factor 11 (GDF11) is a transforming growth factor β superfamily member with a controversial role in aging processes. We have developed a highly specific LC-MS/MS assay to ...quantify GDF11, resolved from its homolog, myostatin (MSTN), based on unique amino acid sequence features. Here, we demonstrate that MSTN, but not GDF11, declines in healthy men throughout aging. Neither GDF11 nor MSTN levels differ as a function of age in healthy women. In an independent cohort of older adults with severe aortic stenosis, we show that individuals with higher GDF11 were more likely to be frail and have diabetes or prior cardiac conditions. Following valve replacement surgery, higher GDF11 at surgical baseline was associated with rehospitalization and multiple adverse events. Cumulatively, our results show that GDF11 levels do not decline throughout aging but are associated with comorbidity, frailty, and greater operative risk in older adults with cardiovascular disease.
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•Immunoplexed liquid chromatography mass spectrometric assessment of GDF11 and MSTN•Circulating GDF11 levels do not change in healthy adults throughout the lifespan•Previous reports of declining GDF11 levels may correspond to changes in MSTN•In CVD, GDF11 is associated with comorbidity, frailty, and post-operative outcomes
Schafer et al. develop a LC-MS/MS assay for precise quantification of GDF11 and its closely related homolog, myostatin, and show that circulating concentrations of GDF11 do not decline in humans during aging. Furthermore, in older adults with cardiovascular disease, increased circulating GDF11 levels are associated with negative health outcomes.
We postulated that locoregional recurrence after limited surgery and radiotherapy for breast cancer might be associated with an additional survival hazard, similar to that of a second primary tumor ...with the same extent of local and regional disease. Using this hypothesis we examined the likely resultant effect on survival. Our calculations indicated that no statistically significant survival deficit due to such recurrence would be detectable until a randomized controlled trial comparing breast conservation with mastectomy had monitored more than 10,000 patients for more than 10 years. A simple mathematical model predicted 5-year survival rates in a cohort of patients treated with breast conservation of 75%, compared to 83% in those without locoregional recurrence. From the date of locoregional recurrence, a 61% 5-year survival rate was predicted, compared to 83% if no hazard was associated with locoregional recurrence. These predictions were compared with the actuarial survival rates of 499 patients with unilateral breast cancer, 49 of whom had developed locoregional recurrence. From the date of initial treatment, the 5-year survival rate of those whose disease recurred was 79%, compared to 88% for those without locoregional recurrence (p = 0.19). The actuarial 5-year survival rate from the date of locoregional recurrence was 63%. The similarity between the patient data and the predictions of the mathematical model indicates that locoregional failure after breast conservation therapy may result in reduced survival. The lack of a significant survival deficit in our cohort or in controlled trials comparing breast conservation therapy with mastectomy is compatible to the small size of the overall effect.
Ph.D. supply VEST, CHARLES M.; RUPP, GEORGE; LANZEROTTI, LOUIS J. ...
Issues in science and technology,
06/1991, Letnik:
7, Številka:
4
Journal Article
Recenzirano
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NMLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
50.
Micheli, Romano Charles M. Atkinson; Noel O’Regan
New Grove Dictionary of Music and Musicians,
2001
Reference
(b Rome, c1575; d Rome, after 1659). Italian composer and music polemicist. He learnt the art of counterpoint from Soriano and G.M. Nanino. He visited various Italian cities including Venice, Naples ...(where he was in the service of Gesualdo from about 1596 to 1598), Ferrara, Bologna and Milan. He became maestro di cappella of Tivoli Cathedral in June 1609 but left under duress in January 1610. He held similar posts at the cathedral of Concordia Sagittaria in 1616 and at Aquileia Cathedral from 1618 to 1621. Returning to Rome, he was favoured for the position of maestro di cappella at the Gesù but his appointment was blocked, probably at the instigation of the papal singers who had been antagonized by his polemics. He responded with a published challenge, the Virtuoso manifesto of 1624. In March 1625 he became maestro of S Luigi dei Francesi, thanks to the intervention of the ambassador of the Duke of Savoy. In July of that year he made his peace with the papal singers, without whose cooperation he could not organize large-scale music at S Luigi or elsewhere, presenting them with a copy of his latest music (presumably the ...
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