In this mixed-methods study, we explored perspectives of ensemble directors (N = 306) regarding standards-based instruction and circumstances impacting standards-based instruction in the areas of ...creating, performing, responding, and connecting. Our research was modeled on Byo’s (1999) examination of teacher perceptions of the implementation of the 1994 music standards. We conducted an initial survey and completed follow-up interviews. Every participant indicated familiarity with the National Core Arts Standards, with many reporting that they regularly addressed standards in their teaching. The anchor standards related to performing were most commonly incorporated, whereas those related to creating and connecting were the least commonly addressed. Teachers shared strategies that promoted standards-based instruction and described barriers that prevented them from fully incorporating standards-based instruction. There is a need for ongoing professional development for in-service teachers, dedicated planning time, and realistic expectations related to the creating, responding, and connecting standards in performing ensembles.
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DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Clinical trials have shown that beta-adrenergic blocking drugs are effective and well tolerated in patients with mild to moderate heart failure, but the utility and safety of these drugs in patients ...with advanced disease have not been evaluated.
We enrolled 56 patients with severe chronic heart failure into a double-blind, placebo-controlled study of the vasodilating beta-blocker carvedilol. All patients had advanced heart failure, as evidenced by a mean left ventricular ejection fraction of 0.16 +/- 0.01 and a mean maximal oxygen consumption of 13.6 +/- 0.6 mL.kg-1.min-1 despite digitalis, diuretics, and an angiotensin-converting enzyme inhibitor (if tolerated). After a 3-week, open-label, up-titration period, 49 of the 56 patients were assigned (in a double-blind fashion using a 2:1 randomization) to receive either carvedilol (25 mg BID, n = 33) or matching placebo (n = 16) for 14 weeks, while background therapy remained constant. Hemodynamic and functional variables were measured at the start and end of the study. Compared with the placebo group, patients in the carvedilol group showed improved cardiac performance, as reflected by an increase in left ventricular ejection fraction (P = .005) and stroke volume index (P = .010) and a decrease in pulmonary wedge pressure, mean right atrial pressure, and systemic vascular resistance (P = .003, .002, and .017, respectively). In addition, compared with placebo, patients treated with carvedilol benefited clinically, as shown by an improvement in symptom scores (P = .002), functional class (P = .013), and submaximal exercise tolerance (P = .006). The combined risk of death, worsening heart failure, and life-threatening ventricular tachyarrhythmia was lower in the carvedilol group than in the placebo group (P = .028), but carvedilol-treated patients had more dizziness and advanced heart block.
Carvedilol produces clinical and hemodynamic improvement in patients who have severe heart failure despite treatment with angiotensin-converting enzyme inhibitors.
In a series of 111 patients with squamous cell carcinoma (SCC), we used immunohistochemistry to examine the expression levels
of four epidermal growth factor receptor (EGFR) family members (EGFR, ...HER-2/neu, HER-3, and HER-4). Expression of the EGFR
members was not significantly associated with tumor size. However, their expressions (except for HER-4) were significantly
associated with the presence of lymph node metastasis, and all of them were significantly associated with distant metastasis.
We further examined the association between the expression levels of the EGFR members and the survival rates in 47 oral SCC
patients whose detailed clinical follow-ups were available. The expression of all EGFR members was significantly associated
with shortened patient survival, and the association was strongest for HER-2/neu. Furthermore, the combination of HER-2, HER-3,
and EGFR but not HER-4 significantly improved the predicting power. The expression level of HER-2/neu was significantly correlated
with that of EGFR or HER-3. Similar coexpression patterns were also observed in three oral SCC cell lines studied, but not
in four other head and neck SCC cell lines. Taken together, these results indicated that expression levels of EGFR, HER-2/neu,
and HER-3 may help predict the outcome of patients with oral SCC.
The aim of the study was to evaluate the diagnostic accuracy of thromboelastometry for assessing rivaroxaban concentrations. The accuracy of thromboelastometry was compared with the high-performance ...liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method, which is the gold standard for drug plasma monitoring (the reference standard). Forty-six clinically stable patients were treated with 10, 15, or 20 mg of rivaroxaban once daily (OD group) or 15 mg twice a day (BID group) (no particular indication for treatment). Patient samples were collected 2 h after the use of the medication (peak) and 2 h before the next dose (trough). The rivaroxaban plasma concentrations were determined via HPLC-MS/MS, and thromboelastometry was performed using a ROTEM® delta analyzer. There were significant prolongations in clotting time (CT) for the 10, 15, and 20 mg of rivaroxaban treatments in the OD groups. In the 15 mg BID group, the responses at the peak and trough times were similar. At the peak times, there was a positive correlation between the plasma concentration of rivaroxaban and CT (Spearman correlation rho=0.788, P<0.001) and clot formation time (rho=0.784, P<0.001), and a negative correlation for alpha angle (rho=-0.771, P<0.001), amplitude after 5 min (rho=-0.763, P<0.001), and amplitude after 10 min (rho=-0.680, P<0.001). The CT presented higher specificity and sensitivity using the cut-off determined by the receiver characteristics curve. ROTEM has potential as screening tool to measure possible bleeding risk associated with rivaroxaban plasma levels.
The cohort consisted of 328 very low birth weight infants (600-1250 g birth weight) who were enrolled in the low-dose prophylactic indomethacin prevention trial and were intraventricular hemorrhage ...(IVH) negative at 6 postnatal hours. The objective was to determine the effects of both IVH and indomethacin on cognitive, language, and achievement performance at 8 years of age.
The cohort was divided into 4 subgroups for analysis: indomethacin plus IVH, indomethacin no IVH, saline plus IVH, and saline with no IVH. The children were evaluated prospectively at 8 years of age with a neurologic assessment, history of school performance, and a battery of cognitive, academic, behavioral, and functional assessments.
Children in both IVH groups had more cerebral palsy; more hearing impairment; lower daily living skills scores; lower IQ, vocabulary, and reading and mathematics achievement test scores; and greater educational resource needs. With logistic regression analyses grade 3 to 4 IVH, periventricular leukomalacia and/or ventriculomegaly, male gender, maternal education, and language spoken in the home contributed to outcomes. No effects of indomethacin or gestational age were identified.
Although biological factors including IVH, ventriculomegaly, and periventricular leukomalacia contribute significantly to school age outcomes among very low birth weight survivors at 8 years of age, social and environmental factors including maternal level of education and primary language spoken in the home are also important contributors to outcome.
The Agency for Healthcare Research and Quality (AHRQ) Smoking Cessation Clinical Practice Guideline recommends that all clinicians strongly advise their patients who use tobacco to quit.
We conducted ...a randomized, controlled trial of the effectiveness of Guideline implementation at eight community-based primary care clinics in southern Wisconsin (four test sites, four control sites) among 2163 consecutively enrolled adult patients who smoked at least one cigarette per day and presented for nonemergency care during the baseline period (June 16, 1999, to June 20, 2000) or the intervention period (from June 21, 2000, to May 3, 2001). After collecting baseline data, staff at test sites implemented the intervention over a 2-month period. The intervention included a tutorial for intake clinicians, group and individual performance feedback for intake clinicians, use of a modified vital signs stamp, an offer of free nicotine replacement therapy, and proactive telephone counseling. Staff at control sites received only general information about the AHRQ Guideline. Self-reported abstinence from smoking was determined by telephone interviews at 2- and 6-month follow-up assessments. Hierarchical logistic regression models were used to estimate the odds ratios (ORs) for treatment assignment after adjustment for patient characteristics. All statistical tests were two-sided.
There were no statistically significant differences in smoking cessation rates between participants at test and control sites during the baseline period. Among participants treated during the intervention period, those at test sites were more likely than those at control sites to report being abstinent at the 2-month (16.4% versus 5.8%; adjusted OR = 3.3, 95% confidence interval CI = 1.9 to 5.6; P<.001) and 6-month (15.4% versus 9.8%; adjusted OR = 1.7, 95% CI = 1.2 to 2.6; P =.009) follow-up assessments and to report continuous abstinence, that is, abstinence at both 2 and 6 months (10.9% versus 3.8%; adjusted OR = 3.4, 95% CI = 1.8 to 6.3; P<.001).
Implementation of a guideline-based smoking cessation intervention by intake clinicians in primary care is associated with higher abstinence among smokers.
Risk for late-onset Alzheimer's disease (LOAD), the most prevalent dementia, is partially driven by genetics. To identify LOAD risk loci, we performed a large genome-wide association meta-analysis of ...clinically diagnosed LOAD (94,437 individuals). We confirm 20 previous LOAD risk loci and identify five new genome-wide loci (IQCK, ACE, ADAM10, ADAMTS1, and WWOX), two of which (ADAM10, ACE) were identified in a recent genome-wide association (GWAS)-by-familial-proxy of Alzheimer's or dementia. Fine-mapping of the human leukocyte antigen (HLA) region confirms the neurological and immune-mediated disease haplotype HLA-DR15 as a risk factor for LOAD. Pathway analysis implicates immunity, lipid metabolism, tau binding proteins, and amyloid precursor protein (APP) metabolism, showing that genetic variants affecting APP and Aβ processing are associated not only with early-onset autosomal dominant Alzheimer's disease but also with LOAD. Analyses of risk genes and pathways show enrichment for rare variants (P = 1.32 × 10
), indicating that additional rare variants remain to be identified. We also identify important genetic correlations between LOAD and traits such as family history of dementia and education.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
In flowering plants, two cells are fertilized in the haploid female gametophyte. Egg and sperm nuclei fuse to form the embryo. A second sperm nucleus fuses with the central cell nucleus, which ...replicates to generate the endosperm, a tissue that supports embryo development. The FERTILIZATION-INDEPENDENT ENDOSPERM (FIE) and MEDEA (MEA) genes encode WD and SET domain polycomb proteins, respectively. In the absence of fertilization, a female gametophyte with a loss-of-function fie or mea allele initiates endosperm development without fertilization. fie and mea mutations also cause parent-of-origin effects, in which the wild-type maternal allele is essential and the paternal allele is dispensable for seed viability. Here, we show that FIE and MEA polycomb proteins interact physically, suggesting that the molecular partnership of WD and SET domain polycomb proteins has been conserved during the evolution of flowering plants. The overlapping expression patterns of FIE and MEA are consistent with their suppression of gene transcription and endosperm development in the central cell as well as their control of seed development after fertilization. Although FIE and MEA interact, differences in maternal versus paternal patterns of expression, as well as the effect of a recessive mutation in the DECREASE IN DNA METHYLATION1 (DDM1) gene on mutant allele transmission, indicate that fie and mea mutations cause parent-of-origin effects on seed development by distinct mechanisms.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
To estimate the incidence of presumed microbial keratitis with and without loss of visual acuity among wearers of a silicone hydrogel contact lens (Lotrafilcon A, Night & Day, CIBA Vision, Inc., ...Duluth, GA), recently approved for up to 30 days of continuous wear.
Prospective cohort postmarket surveillance study.
Contact lens wearers (recruited from 131 practices) who had been prescribed the lens for intended continuous wear of as many as 30 nights.
The occurrence of a corneal infiltrate was ascertained through a combination of center report and direct contact with participants at 3 and 12 months. Whenever a corneal infiltrate was suspected, study and treatment medical records were systematically reviewed by an Endpoints Committee using a predetermined classification scheme for corneal infiltration. Cases of presumed microbial keratitis were determined based on the constellation of presenting signs and symptoms and clinical course.
The incidence of presumed microbial keratitis with and without loss of visual acuity.
A total of 6245 participants were recruited between August 13, 2002 and July 2, 2003. Of these, 4999 subjects (80%) completed 12 months of follow-up, and these participants contributed a total of 5561 person years of lens wearing experience. Approximately 80% of participants routinely wore their lenses continuously for 3 or more weeks. The overall annual rate of presumed microbial keratitis was 18 per 10,000 (95% confidence interval (CI): 8.5-33.1). There were 2 cases of presumed microbial keratitis with loss of visual acuity, an annual rate of 3.6 per 10,000 (95% CI: 0.4-12.9), and an additional 8 cases without loss of visual acuity, an annual rate of 14.4 per 10000 (95% CI: 6.1-28.4). The rate of presumed microbial keratitis was lower for users reporting typical wear of 3 or more weeks than for those wearing the lens for less than a 3-week continuous period (P = 0.02).
The incidence of loss of visual acuity due to microbial keratitis among users of the silicone hydrogel contact lens was low. The overall rate of presumed microbial keratitis with the wearing schedule of as many as 30 nights was similar to that previously reported for conventional extended-wear soft lenses worn for fewer consecutive nights.
Novel scaffolds that bind to serine proteases through a unique network of short hydrogen bonds to the catalytic Ser195 have been developed. The resulting potent serine protease inhibitors were ...designed from lead molecule 2-(2-hydroxyphenyl)1H-benzoimidazole-5-carboxamidine, 6b, which is known to display several modes of binding. For instance, 6b can recruit zinc and bind in a manner similar to that reported by bis(5-amidino-2-benzimidazolyl)methane (BABIM) (Nature 1998, 391, 608−612). Alternatively, 6b can bind in the absence of zinc through a multicentered network of short (<2.3 Å) hydrogen bonds. The lead structure was optimized in the zinc-independent binding mode toward a panel of six human serine proteases to yield optimized inhibitors such as 2-(3-bromo-2-hydroxy-5-methylphenyl)-1H-indole-5-carboxamidine, 22a, and 2-(2-hydroxybiphenyl-3-yl)-1H-indole-5-carboxamidine, 22f. Structure−activity relationships determined that, apart from the amidine function, an indole or benzimidazole and an ortho substituted phenol group were also essential components for optimal potency. The affinities (K i) of 22a and 22f, for example, bearing these groups ranged from 8 to 600 nM toward a panel of six human serine proteases. High-resolution crystal structures revealed that the binding mode of these molecules in several of the enzymes was identical to that of 6b and involved short (<2.3 Å) hydrogen bonds among the inhibitor hydroxyl oxygen, Ser195, and a water molecule trapped in the oxyanion hole. In summation, novel and potent trypsin-like serine protease inhibitors possessing a unique mode of binding have been discovered.
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