30 research outputs found
“The Good Struggle” of Flexible Specificity: Districts Balancing Specific Guidance With Autonomy to Support Standards-Based Instruction
No full textStornaiuolo, A., Desimone, L., & Polikoff, M. (2023). “The Good Struggle” of Flexible Specificity: Districts Balancing Specific Guidance With Autonomy to Support Standards-Based Instruction. American Educational Research Journal, 60(3), 521–561 was originally published in American Educational Research Journal. The version of record is available at: https://doi.org/10.3102/00028312231161037. © 2023 The Author(s). https://journals.sagepub.com/home/aer. Article reuse guidelines: sagepub.com/journals-permissions.This study examines implementation of college-and-career-ready (CCR) education standards across five school districts in Ohio, Texas, California, Pennsylvania, and Massachusetts. Drawing on the policy attributes theory, we found that the specificity of districts’ approaches to two long-recognized policy levers, curriculum and professional learning, was critical in shaping how stakeholders implemented and experienced CCR policies. We identified an approach we called “flexible specificity”—flexibility informed by ongoing data collection and evaluation that allowed districts to develop specific, useful guidance about curriculum and professional learning based on stakeholder needs. We present four shared practices characterizing this approach in two districts, analyzing why those districts seemed to find the right balance of specificity and flexibility while others struggled.Note The research reported here was supported by the Institute of Education Sciences, U.S. Department of Education, through Grant R305C150007. We would like to acknowledge the efforts of the PI Andrew Porter and the research team involved in the data collection and analysis reported here: Meghan Comstock, Adam Edgerton, Nelson Flores, Erica Salvidar Garcia, Shira Haderlein, Jillian Harkins, Phil Nichols, and Katie Pak
An integrative approach to professional development to support college- and career- readiness standards.
No full textThough scholars agree that professional development (PD) is a key mechanism for implementing education policies that call for teacher change, and that PD generally needs to be content-focused, active, collaborative, coherent, and sustained, the application of this framework has yielded mixed results. In this qualitative study, we employed structured interviewing methods to explore how district leaders across five states are implementing college- and career- readiness (CCR) standards across the United States by creatively adapting and integrating the features of this PD framework in order to meet the demands of this mandated educational policy. We illustrate a revised model for how 70 district officials are conceptualizing these features of PD to support CCR standards-based learning
Nightly dosing of regorafenib.
No full text 549 Background: Fatigue and anorexia are major side effects in the use of regorafenib. These effects are compounded in patients with metastatic colon cancer to the liver. Finding a good fit for this agent has been difficult in patients when used in third and fourth line treatments. Our clinic has treated 21 patients with this agent. Methods: After the first four patients’s experienced extreme fatigue and anorexia at the recommended starting dose of 160mg daily, it was decided to start at a 21 day dose of 120mg. Even at this starting dose, it was necessary to dose deescalate. Ten patients were treated at the 120 mg daily dose and escalated 160 mg daily if tolerated. The agent was given at night to take advantage of the sleep period and the diurnal variation in adrenal gland function. No patient was treated with oral corticosteroids. Results: Two patients previously treated and responders were retreated after they decided they would give the agent a second opportunity. One of these patients, on day two of receiving the agent, developed a severe rash and the treatment was stopped. One patient received the agent for one week before he decided to stop, but was experiencing no side effects. Eight patients were eligible for evaluation. All patients had metastatic disease to the liver. Six were treated for at least two months and two were treated only for one month. All therapy was discontinued because of progression of disease. Fatigue and anorexia were evaluated by a change in their ECOG performance status, fatigue criteria and weight change. ECOG performance status of the patients was, ECOG 1, one patient, ECOG 2, six patients, ECOG 3, one patient. The evaluation was done before, during and after each monthly treatment. No patient had a greater than 5% weight loss. Four patients had Grade 1 fatigue, (fatigue relieved by resting). Six of the eight patients were escalated to 160mg daily after two weeks. Conclusions: Although this is a small sample study, it appears that night time dosing may be effective in helping a patient to achieve maximum benefit of regorafenib therapy. This study did not address the changes in absorption caused by a light fat free meal taken at night, and does not take into consideration the possible change in half-life of the agent when taken at night. </jats:p
Abstract 3355: Evaluation of the efficiency of tumor and tissue delivery of carrier mediated agents (CMA) and small molecule (SM) agents in mice using a novel pharmacokinetic (PK) metric relative distribution index over time (RDI-OT).
No full textEvaluation of the efficiency of tumor and tissue delivery of carrier-mediated agents (CMA) and small molecule (SM) agents in mice using a novel pharmacokinetic (PK) metric: relative distribution index over time (RDI-OT)
No full textThe pharmacokinetics (PK) of carrier-mediated agents (CMA) is dependent upon the carrier system. As a result, CMA PK differs greatly from the PK of small molecule (SM) drugs. Advantages of CMAs over SMs include prolonged circulation time in plasma, increased delivery to tumors, increased antitumor response, and decreased toxicity. In theory, CMAs provide greater tumor drug delivery than SMs due to their prolonged plasma circulation time. We sought to create a novel PK metric to evaluate the efficiency of tumor and tissue delivery of CMAs and SMs. We conducted a study evaluating the plasma, tumor, liver, and spleen PK of CMAs and SMs in mice bearing subcutaneous flank tumors using standard PK parameters and a novel PK metric entitled relative distribution over time (RDI-OT), which measures efficiency of delivery. RDI-OT is defined as the ratio of tissue drug concentration to plasma drug concentration at each time point. The standard concentration versus time area under the curve values (AUC) of CMAs were higher in all tissues and plasma compared with SMs. However, 8 of 17 SMs had greater tumor RDI-OT AUC0–last values than their CMA comparators and all SMs had greater tumor RDI-OT AUC0–6 h values than their CMA comparators. Our results indicate that in mice bearing flank tumor xenografts, SMs distribute into tumor more efficiently than CMAs. Further research in additional tumor models that may more closely resemble tumors seen in patients is needed to determine if our results are consistent in different model systems
Paclitaxel, carboplatin, and capecitabine (TCX) with and without radiation in locally advanced and metastatic distal esophageal and esophagogastric junction cancer: A single-center retrospective review.
No full text 197 Background: Toxicities of the active triple-drug DCF regimen (docetaxel, cisplatin and 5-FU) in gastric cancer limit its broad use and general acceptance as first-line therapy. To improve the toxicity profile of triple-drug therapy, distal esophageal and esophagogastric junction (DE-EGJ) poorly differentiated and moderately differentiated adenocarcinoma patients were treated with TCX. This single-center retrospective review is reported for patients treated between 2005 and 2013. Methods: Patients with DE-EGJ adenocarcinoma were treated with capecitabine (850 mg/m2 5 out of 7 or 14 out of 21 days), carboplatin (AUC 5) and paclitaxel (175 mg/m2) every 3 weeks. Those with locally advanced disease received concomitant radiation therapy (50.4 Gy using 3D approach) during the first 2 cycles. Dose reductions (25-50%), delay of therapy and hospitalizations for disease and treatment-related Grades 3/4 toxicities were recorded. Growth factors were prescribed reactively. Kaplan-Meier statistics were used for survival analyses. The institutional tumor registry data provided the historical median survival. Results: Thirty-one males and 3 females (median age 56, range 37-82) with locally advanced (N=17) and metastatic (N=17) disease were included. Median overall survivals are shown below. Two patients were admitted for neutropenic fever and 7 total hospitalizations occurred. Conclusions: A triple-drug combination first-line regimen (TCX) with and without radiation in DE-EGJ cancer is active, and associated with a manageable toxicity profile. The median survival of 15.8 months in patients with metastatic disease treated with TCX compares favorably with the DCF regimen (9.2 mos), the EOX regimen (11.2 mos) as well as institutional historical controls. Our data suggests that future prospective trials evaluating triple-drug regimens in combination with targeted therapy may be feasible in patients with esophageal and gastric adenocarcinoma. [Table: see text] </jats:p
Nanoparticle delivery of a tetravalent E protein subunit vaccine induces balanced, type-specific neutralizing antibodies to each dengue virus serotype.
No full textDengue virus (DENV) is the causative agent of dengue fever and dengue hemorrhagic shock syndrome. Dengue vaccine development is challenging because of the need to induce protection against four antigenically distinct DENV serotypes. Recent studies indicate that tetravalent DENV vaccines must induce balanced, serotype-specific neutralizing antibodies to achieve durable protective immunity against all 4 serotypes. With the leading live attenuated tetravalent DENV vaccines, it has been difficult to achieve balanced and type-specific responses to each serotype, most likely because of unbalanced replication of vaccine viral strains. Here we evaluate a tetravalent DENV protein subunit vaccine, based on recombinant envelope protein (rE) adsorbed to the surface of poly (lactic-co-glycolic acid) (PLGA) nanoparticles for immunogenicity in mice. In monovalent and tetravalent formulations, we show that particulate rE induced higher neutralizing antibody titers compared to the soluble rE antigen alone. Importantly, we show the trend that tetravalent rE adsorbed to nanoparticles stimulated a more balanced serotype specific antibody response to each DENV serotype compared to soluble antigens. Our results demonstrate that tetravalent DENV subunit vaccines displayed on nanoparticles have the potential to overcome unbalanced immunity observed for leading live-attenuated vaccine candidates
Precisely Molded Nanoparticle Displaying DENV-E Proteins Induces Robust Serotype-Specific Neutralizing Antibody Responses.
No full textDengue virus (DENV) is the causative agent of dengue fever and dengue hemorrhagic fever. The virus is endemic in over 120 countries, causing over 350 million infections per year. Dengue vaccine development is challenging because of the need to induce simultaneous protection against four antigenically distinct DENV serotypes and evidence that, under some conditions, vaccination can enhance disease due to specific immunity to the virus. While several live-attenuated tetravalent dengue virus vaccines display partial efficacy, it has been challenging to induce balanced protective immunity to all 4 serotypes. Instead of using whole-virus formulations, we are exploring the potentials for a particulate subunit vaccine, based on DENV E-protein displayed on nanoparticles that have been precisely molded using Particle Replication in Non-wetting Template (PRINT) technology. Here we describe immunization studies with a DENV2-nanoparticle vaccine candidate. The ectodomain of DENV2-E protein was expressed as a secreted recombinant protein (sRecE), purified and adsorbed to poly (lactic-co-glycolic acid) (PLGA) nanoparticles of different sizes and shape. We show that PRINT nanoparticle adsorbed sRecE without any adjuvant induces higher IgG titers and a more potent DENV2-specific neutralizing antibody response compared to the soluble sRecE protein alone. Antigen trafficking indicate that PRINT nanoparticle display of sRecE prolongs the bio-availability of the antigen in the draining lymph nodes by creating an antigen depot. Our results demonstrate that PRINT nanoparticles are a promising platform for delivering subunit vaccines against flaviviruses such as dengue and Zika
