2nd SYMPHONY Research Articles

Remembering Franz Wright

Remembering Franz Wright Elizabeth Oehlkers Wright Click for larger view View full resolution In the ninth month after Franz died, I was asked if I would like to contribute something to a memorial feature in his honor. I was faced with an immediate difficulty involving shared reality. To contribute, I went along with the premise. I slept on the couch for several weeks, facing the chair, the one still there for Franz, to coax out a few of the days I might uniquely offer, private sketches, testing my interest in getting back. There are days that come to me. Some were months or years. Here are a few notes: A day in December the first year we were married and living in Waltham, Franz called me to say he had gotten a job at the independent movie theatre down the street. He said it didn't matter where he was anymore or what he was doing, he could write the poems while sweeping up popcorn. New Year's Eve, a drunk woman wouldn't leave the lobby until someone gave her a light. There was a scene, threats. Franz followed her out. I think Franz introduced the idea to me of driving her forty miles north to Gloucester in an ice storm at 1 a.m. before getting her to come up the stairs and meet me. I recall a congenially rough [End Page 163] voice, apologies, laughing. We left. It was dark in Gloucester of hilly one-way historic streets and none of us knew where her friend lived. How many times passing the same houses, the gas station. And then we were there, her friend opening the door in his socks, a neat votive candle-lit apartment behind him. As a work-study student at the Emerson College Library, I checked out a book for Franz, twice. I knew his name, that he was the translator of The Unknown Rilke, a book I had fallen in love with even after failing the oral presentation for which I bought it. My roommate had Franz for a composition class. She said he read books to them for the entire two-hour period. He put the library book on the counter. I don't remember the title of the book either time. His soft low voice, his downcast eyes; who could blame me if I imagined talking to him alone someday, maybe reading German poems together. When Franz bought us tickets to hear Mahler's 2nd Symphony "The Resurrection" at Symphony Hall in Boston, he typed up the German along with his own synopsis in English then tore these into strips that he handed me at the beginning of each movement. Click for larger view View full resolution On the phone when I was still living in Boston, on the verge of moving in, Franz told me he wanted nothing but to watch baseball with me. I had to borrow a TV. We watched football too, and a lot of movies. Eight years, four apartments later, during the week, after writing alone at home all day, Franz picked me up from my job at the translation agency; we made dinner and sat in the living room to watch the news, then CSI and Law & Order episodes until we couldn't find any more. The next evening we walked to the video store and rented movies, made popcorn, did the dishes, went to bed, things like that. Another evening, a recovery meeting. On the weekends, Franz drove us along the winding 117 from Waltham through to Concord for lunch and a walk in the woods or to our apple orchard and then west on Route 20 until the sun went down. This takes place in eternal time. But there was an end to it. [End Page 164] Click for larger view View full resolution [End Page 165] Year unknown, one weekday evening Franz stretched out on the couch. At the end of the movie: What if you were one time to sit in this chair, I suggested, having been seeing a therapist, and I could stretch out on the couch. Why hadn't I said something sooner—of course! But nobody liked...

Scherzo and the unheimlich: the construct of genre and feeling in the long 19th century

The psychological concept of the uncanny (“das Unheimliche”) has been established in studies by E. Jentsch (1906) and S. Freud (1919). On the grounds of cultural and textual references, which can be found in these studies, one might regard the uncanny as a discourse construct contained in various literary, evaluative, and visual texts stretching from the late 18th century to the First World War. In my paper, I wish to discuss the assumption that the scherzo genre, commonly seen as founded on Haydn’s opus 33 string quartets and coming to a first fruition in various Beethoven cycles shows a particular propensity to act as the musical vehicle for an uncanny quality. The closer scrutiny of two “programmatic” scherzi (those are the 3rd movement of Mahler’s 2nd Symphony and L’Apprenti sorcier by Dukas) might shed light on the advantages of a genre-oriented approach when musical meaning is concerned.

International variation in invasive care of the elderly with acute coronary syndromes

To explore variations in invasive care of the elderly with acute coronary syndromes across international practice. Using combined populations from the SYMPHONY and 2nd SYMPHONY trials, we describe 30-day cardiac catheterization in elderly (> or = 75 years; n = 1794) vs. younger patients (< 75 years; n = 14,043) after multivariable adjustment and by region of enrolment. The use of cardiac catheterization and revascularization were not protocol-specified. Elderly patients (median age 78 years) were more often female and more frequently had hypertension, diabetes, prior myocardial infarction, and prior coronary bypass surgery. Overall, they underwent less cardiac catheterization than younger patients [53 vs. 63%; adjusted OR 0.53 (0.46, 0.60)]. The absolute rate of cardiac catheterization in the elderly varied from 77% (vs. 91% in younger patients) in the US cohort to 27% (vs. 41% in younger patients) in the non-US cohort. Revascularization of elderly who underwent cardiac catheterization was also higher in US than non-US cohorts (71.3 vs. 53.6%). There was a significant interaction between the patient age and the use of catheterization across US and non-US regions of enrolment, as well as differences in the predictors of catheterization in the elderly. Despite these findings, after adjustment, 90-day rates of death and death or myocardial infarction (MI) were not significantly different in elderly who underwent catheterization compared with those who did not. Although older age is universally predictive of lower use of cardiac catheterization, marked variation in catheterization of the elderly exists across international practice. Demonstrated differences in patterns of use suggest a lack of consensus regarding optimal use of an invasive strategy in the elderly.

Prevalence and management of hypertension in acute coronary syndrome patients varies by sex: Observations from the Sibrafiban versus aspirin to Yield Maximum Protection from ischemic Heart events postacute cOroNary sYndromes (SYMPHONY) randomized clinical trials

Hypertension affects 1 billion individuals worldwide and is an independent risk factor for death after acute coronary syndromes (ACS). We examined the prevalence and medical treatment of hypertension among 15,904 ACS patients randomized in the SYMPHONY and 2nd SYMPHONY trials. Analyses were performed overall and according to sex for the United States and across international practice. Multivariable models identified factors associated with use of antihypertensive medication classes and examined the association of hypertension and sex with mortality. In the United States, hypertension was more prevalent in women than in men, overall (63% vs 50%) and within every decile of age. Hypertensive women more often received calcium-channel blockers (35% vs 30%) and diuretics (33% vs 19%) and less often received beta-blockers (51% vs 57%). Angiotensin-converting enzyme inhibitor use was similar (35% vs 34%). Women received multiple agents more frequently than did men: 2 agents, 35% vs 30%; > or = 3 agents, 16% vs 13%. Female sex independently predicted drug-class use only for diuretics. Mortality was higher in hypertensive women than in hypertensive men; after multivariable adjustment, mortality was similar without evidence of a differential association between hypertension and mortality according to sex. Although there was international variation in the use of individual classes of agents, the overall findings by sex were similar across regions. Hypertension is more prevalent in women than in men with ACS, and its medical management varies by sex, but its association with mortality is similar. Opportunities exist to improve medical therapy and outcomes in women with hypertension.

Postmenopausal Hormone Use in Women with Acute Coronary Syndromes

Recent trials reveal no benefit and possible harm from chronic hormone replacement therapy (HRT). Less is known about intermediate-term outcomes associated with HRT use in the setting of acute coronary syndromes (ACS). To examine the prevalence of HRT use and relationships with intermediate-term outcomes among women with ACS, we classified as HRT users or nonusers 4029 postmenopausal women (age > 50 years or postmenopausal by case report form) randomized in the Sibrafiban versus Aspirin to Yield Maximum Protection from Ischemic Heart Events Post-Acute Coronary Syndromes (SYMPHONY) and 2nd SYMPHONY trials. Outcomes included 90-day and 1-year death and 90-day stroke, death, or myocardial infarction (MI); death, MI, or stroke; and death, MI, or severe recurrent ischemia (SRI). HRT use was 13% overall and varied by region (Asia, 0%; Eastern Europe, 0.2%; Latin America, 0.8%; Western Europe, 4%; Australia/New Zealand, 12%; Canada, 14%; United States, 24%); estrogen-only regimens were most common (90%). HRT users were younger, had higher estimated creatinine clearance, more frequently were smokers and had prior revascularization, but less frequently had diabetes, prior angina, or heart failure. Unadjusted 90-day and 1-year mortality rates were lower among HRT users (hazard ratios [95% CI] 0.48 [0.23-0.98] and 0.35 [0.18-0.68], respectively) but after multivariable adjustment, were not significantly different. Ninety-day stroke and composite end points did not differ between HRT users and nonusers. HRT use (predominantly estrogen-only) was low among patients with ACS but varied by region and was not associated with improved intermediate-term outcomes. These results are consistent with the absence of benefit from HRT use (combination or estrogen only) in previous studies in more stable populations.

Incidence and characteristics of stroke during 90-day follow-up in patients stabilized after an acute coronary syndrome

Background Stroke is a rare but serious event that complicates the course of patients with acute coronary syndromes (ACS). The type, outcome, and risk factors of stroke occurring in stabilized patients with ACS have not been previously reported. Methods We evaluated stroke incidence, subtypes, and outcomes, in addition to demographics and clinical risk characteristics associated with stroke among patients enrolled in the Sibrafiban versus Aspirin to Yield Maximum Protection from Ischemic Heart Events Post-acute Coronary Syndromes (SYMPHONY) and 2nd SYMPHONY trials. Results Of 15,904 stabilized patients with ACS, 113 (0.71%) had a stroke over a median follow-up of 90 days. The majority of strokes occurred within 30 days of presentation, and the time course for stroke occurrence paralleled that of myocardial (re)infarction. Most strokes were ischemic (78%), and 52% resulted in moderate or severe disability or death. Patients with stroke were older and more often had hypertension, diabetes, peripheral vascular disease, and atrial fibrillation. Among patients with stroke who had cardiac catheterization, percutaneous coronary intervention, or coronary artery bypass grafting, stroke occurred predominantly after the procedure. No difference in occurrence or type of stroke was observed in the assigned treatment groups. In multivariable modeling age, heart failure, prior stroke, left bundle branch block, and systolic blood pressure predicted the occurrence of stroke. Conclusions In patients stabilized after presenting with a spectrum of ACS and treated with sibrafiban and/or aspirin, stroke occurred in fewer than 1% within 90 days but carried a significant mortality and morbidity risk.

Association of diabetes mellitus and glycemic control strategies with clinical outcomes after acute coronary syndromes

Background Diabetes is associated with an increased risk for coronary artery disease (CAD) and its complications. The relative effect of glucose-lowering strategies of “insulin provision” versus “insulin sensitization” among patients with CAD remains unclear. Methods To evaluate the associations of diabetes and hypoglycemic strategies with clinical outcomes after acute coronary syndromes, we analyzed data from 15,800 patients enrolled in the SYMPHONY and 2nd SYMPHONY trials. Results Compared with nondiabetic patients, patients with diabetes (n = 3101; 19.6%) were older, more often female, more often had prior CAD, hypertension, and hyperlipidemia, and less often were current smokers. The diabetic cohort had higher 90-day unadjusted risk of the composite of death/myocardial infarction (MI)/severe recurrent ischemia (SRI), death/MI, and death alone, as well as a near doubling of 1-year mortality rates. At 1 year, diabetes was associated with significantly higher adjusted risks of death/MI/SRI (OR, 1.3 [95% confidence interval, 1.1, 1.5]) and death/MI (OR, 1.2 [1.0, 1.4]). Hypoglycemic therapy including only insulin and/or sulfonylurea (insulin-providing; n = 1473) was associated with higher 90-day death/MI/SRI compared with therapy that included only biguanide and/or thiazolidinedione therapy (insulin-sensitizing; n = 100) (12.0% vs 5.0%); (adjusted OR, 2.1 [1.2, 3.7]). Conclusions Diabetic patients with acute coronary syndromes had worse clinical outcomes. Although the findings regarding the influence of glycemic-control strategies should be interpreted with caution because of the exploratory nature of the analyses and the relatively small sample size of the insulin-sensitizing group, the improved risk-adjusted outcomes associated with insulin-sensitizing therapy underscore the need to further evaluate treatment strategies for patients with diabetes and CAD.

International variation in the use of evidence-based medicines for acute coronary syndromes.

We sought to evaluate international patterns of use and factors influencing use of evidence-based medications early after ACS. Using a database of 15904 ACS patients enrolled in the SYMPHONY and 2nd SYMPHONY trials in 37 countries, we performed descriptive and logistic regression analyses. After controlling for other factors, region was significantly associated with the use of every class of evidence-based medication, most pronounced for intravenous unfractionated heparin (IV UFH), low-molecular-weight heparin (LMWH), angiotensin II converting enzyme inhibitors (ACEI) and discharge use of lipid-lowering agents. Latin America and Eastern Europe were among the highest users of early ACEI, yet the lowest users of discharge lipid-lowering therapy. Relative to the United States, all regions except Canada had greater use of LMWH and lower use of IV UFH. Compared with patients with acute myocardial infarction, those with unstable angina less often received aspirin, beta-blockers, ACEI, or IV UFH. Older age was associated with lower use of aspirin, beta-blockers, IV UFH, and lipid-lowering agents. Use of evidence-based therapies for management of ACS patients is strongly associated with region. To improve patient outcomes, more research is needed to understand this variation, and to institute appropriate solutions.

Frequency of stent thrombosis after acute coronary syndromes (from the SYMPHONY and 2nd SYMPHONY trials)

We studied stent thrombosis in 4,607 patients with acute coronary syndromes who received a coronary stent as part of routine care during 2 trials of aspirin versus sibrafiban for secondary prevention. In these patients, stent thrombosis occurred more often than in previous patients who underwent elective percutaneous coronary intervention. These patients and their outcomes may be more representative of patients with typical acute coronary syndromes undergoing stenting in clinical practice.

Moderate obesity is associated with better intermediate-term survival in acute coronary syndromes: Results from the SYMPHONY and 2nd SYMPHONY clinical trials

Moderate obesity is associated with better intermediate-term survival in acute coronary syndromes: Results from the SYMPHONY and 2nd SYMPHONY clinical trials

Platelet glycoprotein IIb/IIIa inhibitors: recognition of a two-edged sword?

Glycoprotein (GP) IIb/IIIa antagonists are potent inhibitors of platelet aggregation that provide marked protection from ischemic events in patients undergoing percutaneous coronary intervention (PCI).1,2⇓ Abciximab, the prototypic GP IIb/IIIa inhibitor, has been studied in >8000 patients undergoing elective or high-risk PCI.2,3,4⇓⇓ In these patients, it produces a consistent 35% to 56% reduction in ischemic end points at 30 days, with a significant 22% reduction in the risk of death, as shown in a combined analysis of long-term (3-year minimum) follow-up of the Evaluation of 7E3 for the Prevention of Ischemic Complications (EPIC), Evaluation in PTCA to Improve Long-term Outcome with abciximab GP IIb/IIIa blockade (EPILOG), and Evaluation of Platelet IIb/IIIa Inhibitor for Stenting (EPISTENT) trials.5 Similar results, albeit of a smaller magnitude, have been seen with the small-molecule antagonists tirofiban and eptifibatide, with a 16% to 35% reduction in ischemic events in patients undergoing PCI.1,6⇓ Attempts to expand the therapeutic indication of GP IIb/IIIa antagonists to other conditions associated with platelet-mediated thrombosis, however, have been less fruitful than expected. Instead of reducing major ischemic events, long-term oral GP IIb/IIIa inhibitor therapy7 has uniformly increased the fatality rate. Furthermore, the overall efficacy of a number of the intravenous antagonists in non–ST-segment elevation acute coronary syndromes (ACS), or in combination with thrombolysis in ST-segment elevation myocardial infarction (MI), has been less than anticipated.8 Of particular concern is the fact that there has been a paradoxical increase in adverse events in 2 of the trials of intravenous therapy in ACS.9,10⇓ Platelets are known to play an important role in the pathogenesis of ACS, yet the high levels of platelet inhibition attainable with GP IIb/IIIa antagonists have failed to dramatically improve clinical outcomes outside of PCI. In this article, we discuss these …

La “2a Sinfonia” di Andrej Belyj. Problemi di metodologia e interpretazione

The paper offers an analysis of Andrej Bely's (1880-1934, a Russian Symbolist)2nd Symphony, an original poetic composition in rhythmical prose with numbered verses, probably due to his father's influence, a wellknown mathematician. Analyzing those verses it was possible to show that Bely's imagination, though strongly connected with reality, is able to create colourful linguistic images, which become the mirror of an individual and discontinous inner world. Besides I suggest to apply Florensky's Organoproekcija,where he draws a parallel between the limbs of our body and the instruments created by man’s skill, and I try to apply such criterions to Bely’s Symphony where such an idea seems to be of main importance in order to approach this original composition.

Sibrafiban.

Sibrafiban is the orally administered, nonpeptide, double-prodrug of Ro 44-3888 which is a selective glycoprotein IIb/IIIa receptor antagonist. It is currently undergoing clinical trials for secondary prevention of cardiac events in patients stabilised after acute coronary syndromes. In a phase II dose-finding study (TIMI 12) in patients stabilised after a myocardial infarction (MI) or an episode of unstable angina, there was a dose-dependent inhibition of platelet aggregation which correlated closely with the plasma concentration of the total active drug. An ongoing phase III study (SYMPHONY) compares the effects of sibrafiban on cardiac events with that of aspirin in patients stabilised after a Q wave MI or an episode of unstable angina. This large trial uses twice daily dosage regimens to produce the plasma concentrations which were associated with less bleeding in the earlier dose-ranging trial. A long term (minimum duration 12 months) phase III study (2nd SYMPHONY) is under way to compare the effects of sibrafiban on cardiac events with those of aspirin in patients stabilised after an MI or an episode of unstable angina. The most common adverse events associated with sibrafiban include bleeding, with minor haemorrhages occurring more often than with aspirin.

Oris skladateljstva hrvatskoga glazbenika Ive Prišlina (1902–1941)

Oris skladateljstva hrvatskoga glazbenika Ive Prišlina (1902–1941)

Playing on Words: A Guide to Luciano Berio's Sinfonia

Luciano Berio's Sinfonia (1968) marked a return by the composer to orchestral writing after a gap of six years. This in-depth study demonstrates the central position the work occupies in Berio's output. David Osmond-Smith discusses the way in which Berio used the Bororo myth described in Levi-Strauss's Le cru et le cuit as a framework for Sinfonia. This is one of many influences in the work, which also include Joyce's 'Sirens' chapter from Ulysses, Beckett's The Unnameable and the scherzo from Mahler's 2nd Symphony. The listener who takes refuge in the score of Sinfonia, argues Osmond-Smith, finds there a maze of allusions to things beyond the score. It is some of those allusions that this book seeks to illuminate.