Profiles of Serial Changes in Cardiac Troponin T Concentrations and Outcome in Ambulatory Patients With Chronic Heart Failure

ObjectivesThe purpose of this study was to determine whether different profiles of cardiac troponin T (cTnT) values assessed over time would yield incremental prognostic information on clinically stable outpatients with heart failure (HF).BackgroundcTnT levels were used to estimate prognosis in HF; however, most studies evaluated hospitalized patients using single measurements.MethodsA cohort of 172 New York Heart Association functional class III to IV outpatients was prospectively studied with serial cTnT measurements collected every 3 months over a 2-year period. The primary end point was death or cardiac transplantation, and secondary end points included HF hospitalization.ResultsOf the 172 patients, 22 (13%) died or underwent transplantation during the first year. Therefore, 150 patients were included in the second-year analysis of 3 pre-determined groups: 1) no serial cTnT elevations (defined as <0.01 ng/ml); 2) 1 or more, but not all cTnT values elevated ≥0.01 ng/ml; and 3) all cTnT values elevated during the first year. During the second year, 30 events occurred: 53 patients had persistently normal cTnT levels (<0.01 ng/ml) with 6 primary events (11%); 57 patients had 1 or more but not all cTnT levels elevated with 11 events (19%); 40 patients demonstrated persistently elevated cTnT levels with 13 (33%) primary events (odds ratio: 3.77; 95% confidence interval: 1.28 to 11.07, p = 0.02).ConclusionsElevations in cTnT, even using a low threshold of 0.01 ng/ml, detected during routine clinical follow-up of ambulatory patients with HF, are highly associated with an increased risk of events, particularly with frequent or persistent cTnT elevations of ≥0.01 ng/ml. Therefore, the ability to monitor clinical change through serial cTnT measurements may add to risk assessment in the ambulatory HF population

Examining EC-6 Pre-Service Teachers\u27 Perceptions of Self-Efficacy in Teaching Mathematics

Mathematics teacher quality has become a major focus in national education reform efforts. In addition, there is an increasing interest in the effectiveness of teacher preparation programs and the undergraduate preparation of elementary mathematics teachers. Empirical evidence suggests that teacher attitudes, behaviors and values, or dispositions, towards teaching have a significant impact on student outcomes. The purpose of this study is to survey juniors and seniors in an undergraduate teacher preparation program to gauge their perceptions of self-efficacy and comfort with teaching mathematics. The results have implications for, and reaffirm concerns about the undergraduate preparation of elementary mathematics teachers

Self-care Barriers Reported by Emergency Department Patients With Acute Heart Failure: A Sociotechnical Systems-based Approach

Study objective We pilot tested a sociotechnical systems-based instrument that assesses the prevalence and nature of self-care barriers among patients presenting to the emergency department (ED) with acute heart failure. Methods A semistructured instrument for measuring self-reported self-care barriers was developed and administered by ED clinicians and nonclinician researchers to 31 ED patients receiving a diagnosis of acute heart failure. Responses were analyzed with descriptive statistics and qualitative content analysis. Feasibility was assessed by examining participant cooperation rates, instrument completion times, item nonresponse, and data yield. Results Of 47 distinct self-care barriers assessed, a median of 15 per patient were indicated as “sometimes” or “often” present. Thirty-four specific barriers were reported by more than 25% of patients and 9 were reported by more than 50%. The sources of barriers included the person, self-care tasks, tools and technologies, and organizational, social, and physical contexts. Seven of the top 10 most prevalent barriers were related to patient characteristics; the next 3, to the organizational context (eg, life disruptions). A preliminary feasibility assessment found few item nonresponses or comprehension difficulties, good cooperation, and high data yield from both closed- and open-ended items, but also found opportunities to reduce median administration time and variability. Conclusion An instrument assessing self-care barriers from multiple system sources can be feasibly implemented in the ED. Further research is required to modify the instrument for widespread use and evaluate its implementation across institutions and cultural contexts. Self-care barriers measurement can be one component of broader inquiry into the distributed health-related “work” activity of patients, caregivers, and clinicians

Safety and pharmacokinetics of MM-302, a HER2-targeted antibody–liposomal doxorubicin conjugate, in patients with advanced HER2-positive breast cancer: A phase 1 dose-escalation study

BackgroundThis phase 1 dose-escalation trial studied MM-302, a novel HER2-targeted PEGylated antibody-liposomal doxorubicin conjugate, in HER2-positive locally advanced/metastatic breast cancer.MethodsPatients were enrolled in four cohorts: MM-302 monotherapy (8, 16, 30, 40, and 50 mg/m2 every 4 weeks [q4w]); MM-302 (30 or 40 mg/m2 q4w) plus trastuzumab (4 mg/kg q2w); MM-302 (30 mg/m2) plus trastuzumab (6 mg/kg) q3w; MM-302 (30 mg/m2) plus trastuzumab (6 mg/kg) and cyclophosphamide (450 mg/m2) q3w.ResultsSixty-nine patients were treated. The most common adverse events (AEs) were fatigue and nausea. Grade 3/4 AEs of special interest included neutropenia, fatigue, mucosal inflammation, anemia, thrombocytopenia, febrile neutropenia, and palmar-plantar erythrodysesthesia. The MTD was not reached. With MM-302 ≥ 30 mg/m2, overall response rate (ORR) was 13% and median progression-free survival (mPFS) 7.4 months (95% CI: 3·5-10·9) in all arms. In 25 anthracycline-naïve patients, ORR was 28·0% and mPFS 10·9 months (95% CI: 1·8-15·3). Imaging with 64Cu-labeled MM-302 visualized tumor-drug penetrance in tumors throughout the body, including the brain.ConclusionMM-302 monotherapy, in combination with trastuzumab, or trastuzumab plus cyclophosphamide, was well tolerated and showed promising efficacy. The selected phase 2 MM-302 dose was 30 mg/m2 plus 6 mg/kg trastuzumab q3w

Chronic Stress in Vocational and Intimate Partner Domains as Predictors of Depressive Symptoms After Breast Cancer Diagnosis.

BackgroundAfter cancer diagnosis, depressive symptoms are elevated on average and decline over time, but substantial variability is apparent. Few studies have examined to what extent chronic stress in distinct life domains affects depressive symptoms.PurposeChronic stress in vocational and intimate partner life domains, and their interaction, were tested as predictors of depressive symptoms after breast cancer diagnosis.MethodsWomen (N = 460) completed validated interviews regarding chronic stress in specific life domains shortly after diagnosis and a measure of depressive symptoms every 6 weeks for 6 months.ResultsIn latent growth curve modeling analyses, greater chronic stress in work (b = 2.90; p &lt; .001) and intimate partner domains (b = 1.38, p = .02) was associated with higher depressive symptoms at study entry (intercept), and greater work stress predicted faster recovery from depressive symptoms over time (b = -0.10; p = .01). The two domains of chronic stress also interacted significantly on depressive symptoms at study entry (b = -1.54; p &lt; .02) and over time (b = 0.14; p &lt; .001). Greater work stress was associated with higher depressive symptoms at study entry regardless of intimate partner stress, but greater intimate partner stress was associated with higher depressive symptoms when work stress was low. The decline over 6 months in initially elevated depressive symptoms predicted by high work stress was significantly steeper when intimate partner stress was low.ConclusionsTargeting interventions to recently diagnosed breast cancer patients living with chronically stressful vocational and intimate partner life circumstances could be worthwhile

Disk Loss and Disk Renewal Phases in Classical Be Stars I: Analysis of Long-Term Spectropolarimetric Data

(Abridged) Classical Be stars occasionally transition from having a gaseous circumstellar disk (''Be phase'') to a state in which all observational evidence for the presence of these disks disappears (''normal B-star phase''). We present one of the most comprehensive spectropolarimetric views to date of such a transition for two Be stars, pi Aquarii and 60 Cygni. 60 Cyg's disk loss episode was characterized by a monotonic decrease in emission strength over a time-scale of 1000 days, consistent with the viscous time-scale of the disk, assuming alpha is 0.14. pi Aqr's disk loss was episodic in nature and occurred over a time-scale of 2440 days. An observed time lag between the behavior of the polarization and H-alpha in both stars indicates the disk clearing proceeded in an ''inside-out'' manner. We determine the position angle of the intrinsic polarization to be 166.7 +/- 0.1 degrees for pi Aqr and 107.7 +/- 0.4 degrees for 60 Cyg, and model the observed polarization during the quiescent diskless phase of each star to determine the interstellar polarization along the line of sight. Minor outbursts observed during the quiescent phase of each star shared similar lifetimes as those previously reported for mu Cen, suggesting that the outbursts represent the injection and subsequent viscous dissipation of individual blobs of material into the inner circumstellar environments of these stars. We also observe deviations from the mean intrinsic polarization position angle during polarization outbursts in each star, indicating deviations from axisymmetry. We propose that these deviations might be indicative of the injection (and subsequent circularization) of new blobs into the inner disk, either in the plane of the bulk of the disk material or in a slightly inclined (non-coplanar) orbit.Comment: 30 pages, 14 figures; accepted in Ap

Upregulation of nitric oxide synthase in mice with severe hypoxia-induced pulmonary hypertension

BACKGROUND: The importance of nitric oxide (NO) in hypoxic pulmonary hypertension has been demonstrated using nitric oxide synthase (NOS) knockout mice. In that model NO from endothelial NOS (eNOS) plays a central role in modulating pulmonary vascular tone and attenuating hypoxic pulmonary hypertension. However, the normal regulation of NOS expression in mice following hypoxia is uncertain. Because genetically engineered mice are often utilized in studies of NO, we conducted the present study to determine how hypoxia alters NOS expression in wild-type mice. METHOD: Mice were exposed to sea level, ambient conditions (5280 feet) or severe altitude (17,000 feet) for 6 weeks from birth, and hemodynamics and lung NOS expression were assessed. RESULTS: Hypoxic mice developed severe pulmonary hypertension (right ventricular systolic pressure [RVsP] 60 mmHg) as compared with normoxic mice (27 mmHg). Using quantitative reverse-transcription PCR, it was found that expressions of eNOS and inducible NOS (iNOS) increased 1.5-fold and 3.5-fold, respectively, in the lung. In addition, the level of lung eNOS protein was increased, neuronal NOS (nNOS) protein was unchanged, and iNOS was below the limit of detection. Immunohistochemistry demonstrated no change in lung iNOS or nNOS staining in either central or peripheral areas, but suggested increased eNOS in the periphery following hypoxia. CONCLUSION: In mice, hypoxia is associated with increases in lung eNOS, possibly in iNOS, but not in nNOS; this suggests that the pattern of lung NOS expression following hypoxia must be considered in studies using genetically engineered mice

The Dopamine D 3 Receptor Gene and Posttraumatic Stress Disorder

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108358/1/jts21937.pd

Design and rationale of the high-sensitivity Troponin T Rules Out Acute Cardiac Insufficiency Trial

BACKGROUND: Acute heart failure (AHF) is a common presentation in the Emergency Department (ED), and most patients are admitted to the hospital. Identification of patients with AHF who have a low risk of adverse events and are suitable for discharge from the ED is difficult, and an objective tool would be useful. METHODS: The highly sensitive Troponin T Rules Out Acute Cardiac Insufficiency Trial (TACIT) will enroll ED patients being treated for AHF. Patients will undergo standard ED evaluation and treatment. High-sensitivity troponin T (hsTnT) will be drawn at the time of enrollment and 3 hours after the initial draw. The initial hsTnT draw will be no more than 3 hours after initiation of therapy for AHF (vasodilator, loop diuretic, noninvasive ventilation). Treating clinicians will be blinded to hsTnT results. We will assess whether hsTnT, as a single measurement or in series, can accurately predict patients at low risk of short-term adverse events. CONCLUSION: TACIT will explore the value of hsTnT measurements in isolation, or in combination with other markers of disease severity, for the identification of ED patients with AHF who are at low risk of short-term adverse events