455 research outputs found
Breaking Through the Noise: Literacy Teachers in the Face of Accountability, Evaluation, and Reform
In an era of increased accountability, it is important to understand how exemplary teachers navigate the demands placed on them by their schools, districts, and states in order to support student learning aligned with their beliefs of effective instruction. To understand these negotiations, tensions facing exemplary literacy teachers were examined through a qualitative interview study. Participants included nineteen experienced PK-6th grade teachers from across the U.S. Results of the study indicate that teachers experience discrepancies between their beliefs and state and local mandates, and they discuss a variety of strategies for negotiating these discrepancies. Findings suggest that schools can support effective literacy instruction by cultivating cultures of autonomy for teachers and strengthening teachers’ sense of agency
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Drug-tolerant persister cancer cells are vulnerable to GPX4 inhibition.
Acquired drug resistance prevents cancer therapies from achieving stable and complete responses. Emerging evidence implicates a key role for non-mutational drug resistance mechanisms underlying the survival of residual cancer 'persister' cells. The persister cell pool constitutes a reservoir from which drug-resistant tumours may emerge. Targeting persister cells therefore presents a therapeutic opportunity to impede tumour relapse. We previously found that cancer cells in a high mesenchymal therapy-resistant cell state are dependent on the lipid hydroperoxidase GPX4 for survival. Here we show that a similar therapy-resistant cell state underlies the behaviour of persister cells derived from a wide range of cancers and drug treatments. Consequently, we demonstrate that persister cells acquire a dependency on GPX4. Loss of GPX4 function results in selective persister cell ferroptotic death in vitro and prevents tumour relapse in mice. These findings suggest that targeting of GPX4 may represent a therapeutic strategy to prevent acquired drug resistance
Association of the SULT1A1 R213H polymorphism with colorectal cancer
1. Sulphotransferases are a superfamily of enzymes involved in both detoxification and bioactivation of endogenous and exogenous compounds. The arylsulphotransferase SULT1A1 has been implicated in a decreased activity and thermostability when the wild-type arginine at position 213 of the coding sequence is substituted by a histidine. SULT1A1 is the isoform primarily associated with the conversion of dietary N -OH arylamines to DNA binding adducts and is therefore of interest to determine whether this polymorphism is linked to colorectal cancer. 2. Genotyping, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis, was performed using DNA samples of healthy control subjects (n = 402) and patients with histologically proven colorectal cancer (n = 383). Both control and test populations possessed similar frequencies for the mutant allele (32.1 and 31%, respectively; P = 0.935). Results were not altered when age and gender were considered as potential confounders in a logistic regression analysis. 3. Examination of the sulphonating ability of the two allozymes with respect to the substrates p -nitrophenol and paracetamol showed that the affinity and rate of sulphonation was unaffected by substitution of arginine to histidine at position 213 of the amino acid sequence. 4. From this study, we conclude that the SULT1A1 R213H polymorphism is not linked with colorectal cancer in this elderly Australian population
The characterization of depressive disorders in serious juvenile offenders
The authors systematically evaluated a selected population of juvenile offenders for the prevalence of affective disorders. Seventy-one (40 male, 31 female) serious juvenile offenders were interviewed using the Schedule for Affective Disorders and Schizophrenia (SADS). They were then diagnosed using the Research Diagnostic Criteria (RDC) and the DSM-III. The Hamilton Rating Scales (HRS), Carroll Self-Rating Scale (CSRS), and Global Rating Scale for Depression (GRS) were also obtained for each subject. Eleven (15%) subjects were diagnosed as having an active major depressive disorder (MDDa), 6 (8%) subjects were diagnosed as having a major depressive disorder in remission (MDDr), and 9 (13%) as having a minor depressive disorder (mDD). The HRS, CSRS, and GRS differentiated the MDDa from the other three groups including MDDr, mDD and all other psychiatric diagnoses. RDC subtypes of depressive disorders were identified in those juvenile offenders with active major depressive disorders (MDDa) and compared to a population of hospitalized adolescents with major depressive disorders. There were significant differences in the distribution of the subtypes identified. Secondary, gitated and endogenous subtypes occured significantly more often. The diagnostic, prognostic and therapeutic significance of these findings are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24911/1/0000338.pd
Gait Speed and Mood, Cognition, and Quality of Life in Older Adults With Atrial Fibrillation
Background: Low gait speed has been linked with impaired mood, cognition, and quality of life (QOL) in older adults. We examined whether low gait speed was associated with impaired mood, cognition, and QOL among older adults with atrial fibrillation (AF).
Methods and Results: Participants (n=1185) had a diagnosis of AF, aged \u3e /=65 years, CHA2DS2VASc \u3e /=2 and had no contraindications to anticoagulation. Participants completed a 15-foot walk test, and low gait speed was categorized using cutoffs from the Fried Frailty Index. Participants self-reported measures of depressive symptoms (Patient Health Questionnaire 9 \u3e /=10), anxiety symptoms (Generalized Anxiety Disorder 7 \u3e /=10), cognitive impairment (Montreal Cognitive Assessment \u3c /=23), and potentially impaired Atrial Fibrillation Effect Quality-of-Life Questionnaire \u3c 80. Participants were on average aged 75.3 (SD: 7.0) years, 48.0% were women, and 85.5% were non-Hispanic white; 85.6% were taking an oral anticoagulant, 26.1% had low gait speed, 8.4% had elevated depressive symptoms, 5.7% had elevated anxiety symptoms, 41.1% were cognitively impaired, and 41.6% had potentially impaired AF-related QOL. Participants with low gait speed were significantly more likely to have elevated depressive symptoms (adjusted odds ratio: 2.1, 95% CI: 1.3-3.4), elevated anxiety symptoms (adjusted odds ratio: 2.2, 95% CI: 1.2-3.9), and cognitive impairment (adjusted odds ratio: 1.5, 95% CI: 1.1-2.1). Impaired AF-related QOL did not differ by gait speed after adjustment for clinical characteristics (adjusted odds ratio: 1.1, 95% CI: 0.8-1.5).
Conclusions: Twenty-six percent of older adults with AF had low gait speed, and low gait speed was associated with impaired mood and cognition. Further research is needed to determine whether declines in gait speed lead to impaired mood and cognition or whether these conditions develop concurrently
Improved Survival after Heart Failure: A Community-based Perspective
Background: Heart failure is a highly prevalent, morbid, and costly disease with a poor long-term prognosis. Evidence-based therapies utilized over the past 2 decades hold the promise of improved outcomes, yet few contemporary studies have examined survival trends in patients with acute heart failure.
Objectives: The primary objective of this population-based study was to describe trends in short and long-term survival in patients hospitalized with acute decompensated heart failure (ADHF). A secondary objective was to examine patient characteristics associated with decreased long-term survival.
Methods and Results: We reviewed the medical records of 9,748 patients hospitalized with ADHF at all 11 medical centers in central Massachusetts during 1995, 2000, 2002, and 2004. Patients hospitalized with ADHF were more likely to be elderly and to have been diagnosed with multiple comorbidities in 2004 compared with 1995. Over this period, survival was significantly improved in-hospital, and at 1, 2, and 5 years post-discharge. Five-year survival rates increased from 20% in 1995 to 28% in 2004. Although survival improved substantially over time, older patients and patients with chronic kidney disease, chronic obstructive pulmonary disease, anemia, low body mass index, and low blood pressures had consistently lower post-discharge survival rates than patients without these comorbidities.
Conclusion: Between 1995 and 2004, patients hospitalized with ADHF have become older and increasingly comorbid. Although there has been a significant improvement in survival among these patients, their long-term prognosis remains poor, as fewer than 1 in 3 patients hospitalized with ADHF in 2004 survived more than 5 years
Toward Uniform Implementation Of Parametric Map Digital Imaging And Communication In Medicine Standard In Multisite Quantitative Diffusion Imaging Studies
This paper reports on results of a multisite collaborative project launched by the MRI subgroup of Quantitative Imaging Network to assess current capability and provide future guidelines for generating a standard parametric diffusion map Digital Imaging and Communication in Medicine (DICOM) in clinical trials that utilize quantitative diffusion-weighted imaging (DWI). Participating sites used a multivendor DWI DICOM dataset of a single phantom to generate parametric maps (PMs) of the apparent diffusion coefficient (ADC) based on two models. The results were evaluated for numerical consistency among models and true phantom ADC values, as well as for consistency of metadata with attributes required by the DICOM standards. This analysis identified missing metadata descriptive of the sources for detected numerical discrepancies among ADC models. Instead of the DICOM PM object, all sites stored ADC maps as DICOM MR objects, generally lacking designated attributes and coded terms for quantitative DWI modeling. Source-image reference, model parameters, ADC units and scale, deemed important for numerical consistency, were either missing or stored using nonstandard conventions. Guided by the identified limitations, the DICOM PM standard has been amended to include coded terms for the relevant diffusion models. Open-source software has been developed to support conversion of site-specific formats into the standard representation
Switchbacks, microstreams, and broadband turbulence in the solar wind
Switchbacks are a striking phenomenon in near-Sun coronal hole flows, but their origins, evolution, and relation to the broadband fluctuations seen farther from the Sun are unclear. We use the near-radial lineup of Solar Orbiter and Parker Solar Probe during September 2020 when both spacecraft were in wind from the Sun's Southern polar coronal hole to investigate if switchback variability is related to large scale properties near 1 au. Using the measured solar wind speed, we map measurements from both spacecraft to the source surface and consider variations with source Carrington longitude. The patch modulation of switchback amplitudes at Parker at 20 solar radii was associated with speed variations similar to microstreams and corresponds to solar longitudinal scales of around 5°–10°. Near 1 au, this speed variation was absent, probably due to interactions between plasma at different speeds during their propagation. The alpha particle fraction, which has recently been shown to have spatial variability correlated with patches at 20 solar radii, varied on a similar scale at 1 au. The switchback modulation scale of 5°–10°, corresponding to a temporal scale of several hours at Orbiter, was present as a variation in the average deflection of the field from the Parker spiral. While limited to only one stream, these results suggest that in coronal hole flows, switchback patches are related to microstreams, perhaps associated with supergranular boundaries or plumes. Patches of switchbacks appear to evolve into large scale fluctuations, which might be one driver of the ubiquitous turbulent fluctuations in the solar wind
The effects of lower-body compression garments on walking performance and perceived exertion in adults with CVD risk factors
Objectives
Compression garments are used by athletes in attempts to enhance performance and recovery, although evidence to support their use is equivocal. Reducing the exertion experienced during exercise may encourage sedentary individuals to increase physical activity. The aim of this study was to assess the effect of compression garments on walking performance (self-paced and enforced pace) and rate of perceived exertion (RPE) in adults who presented with two or more CVD risk factors. Participants (n = 15, 10 female, 58.9 ± 11.5 years, BMI 27.5 ± 4.5 kg m2) were recruited.
Design
A repeated measures design.
Methods
Participants were randomised to Modified Bruce Protocol (enforced pace), or the 6 min walk test (self-paced), and completed the test wearing compression garments or normal exercise clothes (Control). Outcome measures included stage completed, gross efficiency (%) and RPE in Modified Bruce Protocol, and distance walked (m) and RPE in 6 min walk test.
Results
In the Modified Bruce Protcol participants had a higher RPE (15.5 ± 2.5 vs 14.3 ± 2.2) and a lower efficiency (19.1 ± 5.9 vs 21.1 ± 6.7) in the compression garment condition compared with control, p < 0.05. In the 6 min walk test participants walked 9% less in the compression garment condition (p < 0.05) but did not have a lower RPE.
Conclusions
Compared with previous studies reporting enhanced or no effects of compression garments on performance or RPE, this study shows adverse effects of such clothing in untrained individuals with CVD risk factors. The mechanisms underlying this negative effect require further exploration. Use of garments designed for the athletic individuals may not be suitable for the wider population
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