Opportunity and Equity: Enrollment and Outcomes of Black and Latino Males in Boston Public Schools

Boston Public School (BPS) leaders commissioned this study to examine patterns of enrollment, access, engagement, and performance of Black and Latino males from School Year 2009 to School Year 2012. This quantitative analysis constitutes Phase I of a larger study that will ultimately include qualitative case studies examining promising practices in BPS schools in which Black and Latino males perform well

Elementary Teachers’ Verbal Support of Engineering Integration in an Interdisciplinary Project

Despite emphasis on authentic science, technology, engineering, mathematics, and computer science (STEM+CS) projects in classrooms, research continues to demonstrate opportunity gaps in learning STEM+CS for students with disabilities. This study investigates how teachers verbally support students in two differently tracked classrooms to engage in engineering lessons that integrate science and computer science. Specifically, this study explores how the same elementary teachers both implicitly and explicitly support students across two classroom contexts, one class section with a larger proportion of students who were tracked into accelerated mathematics and another class section with a larger proportion of students with individualized educational plans (IEPs). Transcripts of whole-class discussion were analyzed for interdisciplinary instructional moves in which teachers verbally supported the integration of disciplines to help students to engage in interdisciplinary activities. Findings reveal that all of the interdisciplinary instructional moves were implicit for the class section with a large proportion of students in advanced mathematics while most were explicit for the class section with students with IEPs, and that most of the interdisciplinary instructional moves were added by the teachers rather than planned in the curriculum materials. Most commonly, teachers added interdisciplinary instructional moves between computer science and engineering. Implications of this study include recommendations for support that teachers need to engage in the important, but challenging, work of integrating science and computer science practices through engineering lessons within elementary science classrooms. This study adds to a growing understanding of equitable learning opportunities in interdisciplinary learning through engineering for elementary students

Protein Delivery of an Artificial Transcription Factor Restores Widespread Ube3a Expression in an Angelman Syndrome Mouse Brain.

Angelman syndrome (AS) is a neurological genetic disorder caused by loss of expression of the maternal copy of UBE3A in the brain. Due to brain-specific genetic imprinting at this locus, the paternal UBE3A is silenced by a long antisense transcript. Inhibition of the antisense transcript could lead to unsilencing of paternal UBE3A, thus providing a therapeutic approach for AS. However, widespread delivery of gene regulators to the brain remains challenging. Here, we report an engineered zinc finger-based artificial transcription factor (ATF) that, when injected i.p. or s.c., crossed the blood-brain barrier and increased Ube3a expression in the brain of an adult mouse model of AS. The factor displayed widespread distribution throughout the brain. Immunohistochemistry of both the hippocampus and cerebellum revealed an increase in Ube3a upon treatment. An ATF containing an alternative DNA-binding domain did not activate Ube3a. We believe this to be the first report of an injectable engineered zinc finger protein that can cause widespread activation of an endogenous gene in the brain. These observations have important implications for the study and treatment of AS and other neurological disorders

Mellowing skeptical consumers: An examination of sponsorship-linked advertising

This research provides insight into the complex relationship between consumer response to persuasion attempts and skepticism, suggesting that erstwhile targets may be swayed by campaigns pitched as a form of entertainment. The authors examine consumer responses to an important sponsorship-leveraging tool: sponsorship-linked advertising (SLA). A theoretical model of consumer response to SLA is proposed, drawing on important resistance mechanisms to persuasion, including ad skepticism, attributed advertiser motives, and the nature of thoughts. Results confirm existing research on consumer skepticism suggesting its transitory nature and hence potential for advertisers to strategically temper it through specific cues in ad execution. Differential processing between SLA and traditional advertising is supported, such that SLA elicits more favorable cognitive response

Is There Any Interaction Between Sex and Renal Function Change During Hospital Stay in Patients Hospitalized With Acute Heart Failure?

Background: Renal dysfunction is a strong predictor of outcomes in patients with acute heart failure (AHF). However. less is known about how sex may influence the prognostic import of renal function in AHF. Methods and Results: In a post hoc analysis of the ASCEND-HF trial including 5377 patients with AHF (33% female), patients were categorized into 3 groups based on the changes in renal function during their hospital stay. Worsening. stable, and improving renal functions were defined as a >= 20% decrease, a = 20% increase in the estimated glomentlar filtration rate, respectively. The primary outcome was the composite of 30-day all-cause mortality or HF rehospitalization. The median baseline and discharge estimated glomerular filtration rate were 58.4 and 56.9 mL/min/l.73 m(2), respectively. Worsening, stable, and improving renal function was observed in 31.9%, 63.2, and 4.9% of patients. respectively. Worsening renal function was associated with adverse outcomes at 30 days (adjusted hazard ratio [aHR] 1.47, 95% confidence interval [CI] 1.22-1.76). This association existed in both males and females (aHR 1.42 and aHR 1.56, respectively, both P < .01). There was an interaction between renal function changes and sex (P = .025), because improving renal function was associated with better outcomes in men(aHR 0.29, 95% CI 0.13 0.66) as compared with women (aHR 1.18, 95% CI 0.59 2.35). There was no interaction between the ejection fraction and renal function in association with subsequent outcomes. Conclusions: Irrespective of sex, worsening renal function was associated with poorer outcomes at 30 days in patients with AHF. More studies are warranted to further delineate the possible sex differences in this setting

The Alberta Heart Failure Etiology and Analysis Research Team (HEART) study

Background Nationally, symptomatic heart failure affects 1.5-2% of Canadians, incurs $3 billion in hospital costs annually and the global burden is expected to double in the next 1–2 decades. The current one-year mortality rate after diagnosis of heart failure remains high at >25%. Consequently, new therapeutic strategies need to be developed for this debilitating condition. Methods/Design The objective of the Alberta HEART program (http://albertaheartresearch.ca) is to develop novel diagnostic, therapeutic and prognostic approaches to patients with heart failure with preserved ejection fraction. We hypothesize that novel imaging techniques and biomarkers will aid in describing heart failure with preserved ejection fraction. Furthermore, the development of new diagnostic criteria will allow us to: 1) better define risk factors associated with heart failure with preserved ejection fraction; 2) elucidate clinical, cellular and molecular mechanisms involved with the development and progression of heart failure with preserved ejection fraction; 3) design and test new therapeutic strategies for patients with heart failure with preserved ejection fraction. Additionally, Alberta HEART provides training and education for enhancing translational medicine, knowledge translation and clinical practice in heart failure. This is a prospective observational cohort study of patients with, or at risk for, heart failure. Patients will have sequential testing including quality of life and clinical outcomes over 12 months. After that time, study participants will be passively followed via linkage to external administrative databases. Clinical outcomes of interest include death, hospitalization, emergency department visits, physician resource use and/or heart transplant. Patients will be followed for a total of 5 years. Discussion Alberta HEART has the primary objective to define new diagnostic criteria for patients with heart failure with preserved ejection fraction. New criteria will allow for targeted therapies, diagnostic tests and further understanding of the patients, both at-risk for and with heart failure

Glucose Depletion in the Airway Surface Liquid Is Essential for Sterility of the Airways

Diabetes mellitus predisposes the host to bacterial infections. Moreover, hyperglycemia has been shown to be an independent risk factor for respiratory infections. The luminal surface of airway epithelia is covered by a thin layer of airway surface liquid (ASL) and is normally sterile despite constant exposure to bacteria. The balance between bacterial growth and killing in the airway determines the outcome of exposure to inhaled or aspirated bacteria: infection or sterility. We hypothesized that restriction of carbon sources –including glucose– in the ASL is required for sterility of the lungs. We found that airway epithelia deplete glucose from the ASL via a novel mechanism involving polarized expression of GLUT-1 and GLUT-10, intracellular glucose phosphorylation, and low relative paracellular glucose permeability in well-differentiated cultures of human airway epithelia and in segments of airway epithelia excised from human tracheas. Moreover, we found that increased glucose concentration in the ASL augments growth of P. aeruginosa in vitro and in the lungs of hyperglycemic ob/ob and db/db mice in vivo. In contrast, hyperglycemia had no effect on intrapulmonary bacterial growth of a P. aeruginosa mutant that is unable to utilize glucose as a carbon source. Our data suggest that depletion of glucose in the airway epithelial surface is a novel mechanism for innate immunity. This mechanism is important for sterility of the airways and has implications in hyperglycemia and conditions that result in disruption of the epithelial barrier in the lung

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.