Preparing Teachers: Highly Qualified to Do What? Editors’ introduction

The No Child Left Behind Act of 2001 has had significant effects on teacher preparation programs, both in terms of changes required for policy compliance and through important program adjustments. These adjustments have largely been made in response to changes in partner schools and districts, where pacing guides, scripted curricula, benchmark testing and program improvement mandates are now the norm. In the context of anticipated robust policy activity in K-12 education and teacher education (e.g., possible re-authorization of the Elementary and Secondary Education Act, adoption of the Common Core Standards, new teacher certification performance assessments, etc.), it is important to understand the ways in which the current federal law, focused primarily on K-12 education, has also shaped teacher preparation programs. Paying attention to the dynamics involved in such context that his article introduces the articles of EPAA/AAPE’s Special Issue on Preparing Teachers: Highly Qualified to Do What

Immunomodulatory Roles of CTRP3 in Endotoxemia and Metabolic Stress

C1q/TNF-related protein 3 (CTRP3) is a secreted hormone that modulates hepatic glucose and lipid metabolism. Its circulating levels are reduced in human and rodent models of obesity, a metabolic state accompanied by chronic low-grade inflammation. Recent studies have demonstrated an anti-inflammatory role for recombinant CTRP3 in attenuating LPS-induced systemic inflammation, and its deficiency markedly exacerbates inflammation in a mouse model of rheumatoid arthritis. We used genetic mouse models to explore the immunomodulatory function of CTRP3 in response to acute (LPS challenge) and chronic (high-fat diet) inflammatory stimuli. In a sublethal dose of LPS challenge, neither CTRP3 deficiency nor its overexpression in transgenic mice had an impact on IL-1β, IL-6, TNF-α, or MIP-2 induction at the serum protein or mRNA levels, contrary to previous findings based on recombinant CTRP3 administration. In a metabolic context, we measured 71 serum cytokine levels in wild-type and CTRP3 transgenic mice fed a high-fat diet or a matched control low-fat diet. On a low-fat diet, CTRP3 transgenic mice had elevated circulating levels of multiple chemokines (CCL11, CXCL9, CXCL10, CCL17, CX3CL1, CCL22 and sCD30). However, when obesity was induced with a high-fat diet, CTRP3 transgenic mice had lower circulating levels of IL-5, TNF-α, sVEGF2, and sVEGFR3, and a higher level of soluble gp130. Contingent upon the metabolic state, CTRP3 overexpression altered chemokine levels in lean mice, and attenuated systemic inflammation in the setting of obesity and insulin resistance. These results highlight a context-dependent immunomodulatory role for CTRP3

Rates of Potentially Inappropriate Dosing of Direct-Acting Oral Anticoagulants and Associations With Geriatric Conditions Among Older Patients With Atrial Fibrillation: The SAGE-AF Study

Background: Direct-acting oral anticoagulant (DOAC) dosing guidelines for atrial fibrillation recommend dose alteration based on age, renal function, body weight, and drug-drug interactions. There is paucity of data describing the frequency and factors associated with prescription of potentially inappropriate doses. Methods and Results: In the ongoing SAGE-AF (Systematic Assessment of Geriatric Elements in Atrial Fibrillation) study, we performed geriatric assessments (frailty, cognitive impairment, sensory impairments, social isolation, and depression) for participants with atrial fibrillation (age \u3e /=65 years, CHA2DS2VASc \u3e /=2, no anticoagulant contraindications). We developed an algorithm to analyze DOAC dose appropriateness accounting for drug-drug interactions, age, renal function, and body weight. We also examined whether geriatric impairments were related to inappropriate dosing. Of 1064 patients prescribed anticoagulants, 460 received a DOAC. Participants were aged 74+/-7 years, 49% were women, and 82% were white. A quarter (23%; n=105) of participants received inappropriate DOAC dose, of whom 82 (78%) were underdosed and 23 (22%) were overdosed. Among participants receiving an inappropriate dose, 12 (11%) were identified using the drug-drug interactions criteria and would have otherwise been misclassified. In multivariable regression analyses, older age, higher CHA2DS2VASc score, and history of renal failure were associated with inappropriate DOAC dosing (P \u3c 0.05). Geriatric conditions were not associated with inappropriate dosing. Conclusions: In this cohort, over 20% of older patients with atrial fibrillation treated with DOACs were prescribed an inappropriate dose, with most being underdosed. Drug-drug interactions were common. Factors that influence prescription of guideline-nonadherent doses may be perception of higher bleeding risk or presence of renal failure in addition to lack of familiarity with dosing guidelines

Comparative Transcriptional Network Modeling of Three PPAR-α/γ Co-Agonists Reveals Distinct Metabolic Gene Signatures in Primary Human Hepatocytes

Aims: To compare the molecular and biologic signatures of a balanced dual peroxisome proliferator-activated receptor (PPAR)-α/γ agonist, aleglitazar, with tesaglitazar (a dual PPAR-α/γ agonist) or a combination of pioglitazone (Pio; PPAR-γ agonist) and fenofibrate (Feno; PPAR-α agonist) in human hepatocytes. Methods and Results: Gene expression microarray profiles were obtained from primary human hepatocytes treated with EC50-aligned low, medium and high concentrations of the three treatments. A systems biology approach, Causal Network Modeling, was used to model the data to infer upstream molecular mechanisms that may explain the observed changes in gene expression. Aleglitazar, tesaglitazar and Pio/Feno each induced unique transcriptional signatures, despite comparable core PPAR signaling. Although all treatments inferred qualitatively similar PPAR-α signaling, aleglitazar was inferred to have greater effects on high- and low-density lipoprotein cholesterol levels than tesaglitazar and Pio/Feno, due to a greater number of gene expression changes in pathways related to high-density and low-density lipoprotein metabolism. Distinct transcriptional and biologic signatures were also inferred for stress responses, which appeared to be less affected by aleglitazar than the comparators. In particular, Pio/Feno was inferred to increase NFE2L2 activity, a key component of the stress response pathway, while aleglitazar had no significant effect. All treatments were inferred to decrease proliferative signaling. Conclusions: Aleglitazar induces transcriptional signatures related to lipid parameters and stress responses that are unique from other dual PPAR-α/γ treatments. This may underlie observed favorable changes in lipid profiles in animal and clinical studies with aleglitazar and suggests a differentiated gene profile compared with other dual PPAR-α/γ agonist treatments

Planck and reionization history: a model selection view

We use Bayesian model selection tools to forecast the Planck satellite's ability to distinguish between different models for the reionization history of the Universe, using the large angular scale signal in the cosmic microwave background polarization spectrum. We find that Planck is not expected to be able to distinguish between an instantaneous reionization model and a two-parameter smooth reionization model, except for extreme values of the additional reionization parameter. If it cannot, then it will be unable to distinguish between different two-parameter models either. However, Bayesian model averaging will be needed to obtain unbiased estimates of the optical depth to reionization. We also generalize our results to a hypothetical future cosmic variance limited microwave anisotropy survey, where the outlook is more optimistic.Comment: 6 pages, 15 figures in MNRAS style, minor changes to match accepted versio

Gene expression profiling in NOD mice reveals that B cells are highly educated by the pancreatic environment during autoimmune diabetes

Aims/hypothesis: B cells play an important role in driving the development of type 1 diabetes; however, it remains unclear how they contribute to local beta cell destruction during disease progression. Here, we use gene expression profiling of B cell subsets identified in inflamed pancreatic tissue to explore their primary functional role during the progression of autoimmune diabetes. Methods: Transcriptional profiling was performed on FACS-sorted B cell subsets isolated from pancreatic islets and the pancreatic lymph nodes of NOD mice. Results: B cells are highly modified by the inflamed pancreatic tissue and can be distinguished by their transcriptional profile from those in the lymph nodes. We identified both a discrete and a core shared gene expression profile in islet CD19+CD138– and CD19+CD138+ B cell subsets, the latter of which is known to have enriched autoreactivity during diabetes development. On localisation to pancreatic islets, compared with CD138– B cells, CD138+ B cells overexpress genes associated with adhesion molecules and growth factors. Their shared signature consists of gene expression changes related to the differentiation of antibody-secreting cells and gene regulatory networks associated with IFN signalling pathways, proinflammatory cytokines and Toll-like receptor (TLR) activation. Finally, abundant TLR7 expression was detected in islet B cells and was enhanced specifically in CD138+ B cells. Conclusions/interpretation: Our study provides a detailed transcriptional analysis of islet B cells. Specific gene signatures and interaction networks have been identified that point towards a functional role for B cells in driving autoimmune diabetes. Graphical abstract

New Generation of Educators Initiative: Transforming teacher preparation.

The focus of the New Generation of Educators Initiative (NGEI) was to answer the question "What would it take to transform teacher education?" From 2016 to 2019, with support from the S. D. Bechtel, Jr. Foundation, teacher education programs at 10 California State University (CSU) campuses partnered with local school districts to design and demonstrate innovative practices that could transform teacher preparation. This report documents the learnings from multiple participants in this transformative work, including Foundation program staff and representatives from partnerships between universities and school districts

Right Atrial Pressure Affects the Interaction between Lung Mechanics and Right Ventricular Function in Spontaneously Breathing COPD Patients

INTRODUCTION: It is generally known that positive pressure ventilation is associated with impaired venous return and decreased right ventricular output, in particular in patients with a low right atrial pressure and relative hypovolaemia. Altered lung mechanics have been suggested to impair right ventricular output in COPD, but this relation has never been firmly established in spontaneously breathing patients at rest or during exercise, nor has it been determined whether these cardiopulmonary interactions are influenced by right atrial pressure. METHODS: Twenty-one patients with COPD underwent simultaneous measurements of intrathoracic, right atrial and pulmonary artery pressures during spontaneous breathing at rest and during exercise. Intrathoracic pressure and right atrial pressure were used to calculate right atrial filling pressure. Dynamic changes in pulmonary artery pulse pressure during expiration were examined to evaluate changes in right ventricular output. RESULTS: Pulmonary artery pulse pressure decreased up to 40% during expiration reflecting a decrease in stroke volume. The decline in pulse pressure was most prominent in patients with a low right atrial filling pressure. During exercise, a similar decline in pulmonary artery pressure was observed. This could be explained by similar increases in intrathoracic pressure and right atrial pressure during exercise, resulting in an unchanged right atrial filling pressure. CONCLUSIONS: We show that in spontaneously breathing COPD patients the pulmonary artery pulse pressure decreases during expiration and that the magnitude of the decline in pulmonary artery pulse pressure is not just a function of intrathoracic pressure, but also depends on right atrial pressure

The Future of Child and Adolescent Clinical Psychopharmacology: A Systematic Review of Phase 2, 3, or 4 Randomized Controlled Trials of Pharmacologic Agents Without Regulatory Approval or for Unapproved Indications

The pace of development and implementation of novel medications in child and adolescent psychiatry has remained slow. We systematically searched https://clinicaltrials.gov/ and https://www.clinicaltrialsregister.eu/ (from 01/01/2010 to 08/23/2022) for phase 2 or 3 randomized controlled trials (RCTs) of medications without regulatory approval in the US, Europe or Asia. We also included RCTs of dietary interventions/probiotics. Additionally, we searched phase 4 RCTs of agents targeting unlicensed indications for children/adolescents with mental health disorders. We retrieved 234 ongoing or completed RCTs, including 26 (11%) with positive findings on ≥1 primary outcome, 43 (19%) with negative/unavailable results on every primary outcome, and 165 (70%) without publicly available statistical results. The only two compounds with evidence of significant effects that were replicated in ≥1 additional RCT without any negative RCTs were dasotraline for attention-deficit/hyperactivity disorder, and carbetocin for hyperphagia in Prader-Willi syndrome. Among other strategies, targeting specific symptom dimensions in samples stratified based on clinical characteristics or established biomarkers may increase chances of success in future development programmes