Managing for Change: Achieving Systemic Reform Through the Effective Implementation of Networks for School Improvement

In August 2018, the Bill & Melinda Gates Foundation (“the foundation”) launched its Networks for School Improvement (NSIs) initiative. To further its own continuous learning as well as the learning of its grantees and the educational field, the foundation engaged the Center for Public Research and Leadership (CPRL) to conduct a formative evaluation of the NSIs initiative during its first two years. The research questions that guided this study were: How are network hubs implementing the Network for School Improvement (NSI) strategy? What are the characteristics of effective networks and network hubs? To answer these questions, CPRL used a qualitative research design to deeply explore the work of nine networks representative of the broader pool of grantees. Selection was designed to ensure diversity with respect to the following characteristics: (a) geographic location, (b) number of schools in the network, (c) number of districts in the network, (d) grade band targeted, and (e) problem of practice. The findings presented in this paper emerge from an analysis of data collected from these networks across two years. In total, CPRL conducted over 160 interviews, observed 22 network convenings, and analyzed nearly 1,000 artifacts and documents

Susceptibility to chronic mucus hypersecretion, a genome wide association study

Background: Chronic mucus hypersecretion (CMH) is associated with an increased frequency of respiratory infections, excess lung function decline, and increased hospitalisation and mortality rates in the general population. It is associated with smoking, but it is unknown why only a minority of smokers develops CMH. A plausible explanation for this phenomenon is a predisposing genetic constitution. Therefore, we performed a genome wide association (GWA) study of CMH in Caucasian populations.Methods: GWA analysis was performed in the NELSON-study using the Illumina 610 array, followed by replication and metaanalysis in 11 additional cohorts. In total 2,704 subjects with, and 7,624 subjects without CMH were included, all current or former heavy smokers (&gt;= 20 pack-years). Additional studies were performed to test the functional relevance of the most significant single nucleotide polymorphism (SNP).Results: A strong association with CMH, consistent across all cohorts, was observed with rs6577641 (p = 4.25610(-6), OR = 1.17), located in intron 9 of the special AT-rich sequence-binding protein 1 locus (SATB1) on chromosome 3. The risk allele (G) was associated with higher mRNA expression of SATB1 (4.3610 29) in lung tissue. Presence of CMH was associated with increased SATB1 mRNA expression in bronchial biopsies from COPD patients. SATB1 expression was induced during differentiation of primary human bronchial epithelial cells in culture.Conclusions: Our findings, that SNP rs6577641 is associated with CMH in multiple cohorts and is a cis-eQTL for SATB1, together with our additional observation that SATB1 expression increases during epithelial differentiation provide suggestive evidence that SATB1 is a gene that affects CMH.</p

Offering to Return Results to Research Participants: Attitudes and Needs of Principal Investigators in the Children\u27s Oncology Group

PURPOSE: The offer to return a summary of results to participants after the conclusion of clinical research has many potential benefits. The authors determined current practice and attitudes and needs of researchers in establishing programs to return results to research participants. METHODS: An Internet survey of all 236 principal investigators (PIs) of the Children\u27s Oncology Group in May 2002 recorded PI and institutional demographics, current practice, and perceived barriers to and needs of PIs for the creation of research results programs. RESULTS: One hundred fifty (63.8%) PIs responded. Few institutions (n = 5) had established, comprehensive programs to offer the return of results. PIs indicated that major impediments to the implementation of such programs are the preparation of lay summaries, time constraints, the task of contacting participants, and potential distress for the participants. PIs identified the following facilitators to the establishment of a program in their own institution: lay summaries, web site, preparation of an oncologist\u27s summary, and financial credits. There was no clear consensus as to when the results should be shared: 30% indicated after the study was closed and 24% indicated at the time of publication of results. A substantial proportion of respondents opposed or strongly opposed the implementation of a universal offering of results to research participants. CONCLUSIONS: Few Children\u27s Oncology Group institutions have programs that offer the return of results to research participants. Significant barriers and facilitators to this process have been identified

Sexual harassment

To the Editor: The Special Article by Phillips and Schneider (Dec. 23 issue)1 addresses what they define as sexual harassment of female doctors by patients. Sexual harassment is usually defined as the creation of a hostile atmosphere or abuse of a position of power in a relationship through sexual behavior or language. Since the relationship between doctor and patient invests the doctor with most of the power, it seems intrinsically contradictory to define the behavior described by Phillips and Schneider as harassment. The puritanical attitude that all sexual language and behavior constitute harassment has impaired the effectiveness of the medical. © 1994, Massachusetts Medical Society. All rights reserved.SCOPUS: le.jinfo:eu-repo/semantics/publishe

Pathophysiology of Hemolysis in Infections with Hemophilus influenzae Type b

Abstract The capsular polysaccharide of Hemophilus influenzae type b, polyribosyl ribitol phosphate (PRP), is released from growing organisms during human infection and can be found in body fluids. It binds to untreated erythrocytes. Many patients with invasive infections with this organism develop significant hemolysis, but the mechanism has been unclear. We have found that PRP binds to human erythrocytes in vivo. PRP-coated erythrocytes have a shortened circulation time in mice, but do not lyse spontaneously or fix complement. PRP-coated erythrocytes exposed to antiserum to H. influenzae type b are undamaged in the absence of complement, but are rapidly and effectively lysed in the presence of an intact complement system both in vitro and in vivo in mice. PRP-coated red cells are taken up by liver and spleen. Antiserum to PRP increases hepatic uptake of PRP-coated red cells more than splenic, and appears to induce intravascular, complementmediated hemolysis, as well as extravascular hemolysis. Patients with invasive infection develop hemolysis when circulating PRP and antibody to PRP are present simultaneously. PRP can sometimes be detected on patient erythrocytes when free PRP is present in serum, but this is an inconsistent finding. The hemolytic anemia that occurs during human infection with H. influenzae type b may be due to absorption of PRP to red cells and immune destruction of sensitized erythrocytes. The process requires an intact complement system; both complement-mediated cell lysis and extravascular hemolysis contribute to red cell destruction

ELISPOT Assay for Monitoring Cytotoxic T Lymphocytes (CTL) Activity in Cancer Vaccine Clinical Trials

The profiling and monitoring of immune responses are key elements in the evaluation of the efficacy and development of new biotherapies, and a number of assays have been introduced for analyzing various immune parameters before, during, and after immunotherapy. The choice of immune assays for a given clinical trial depends on the known or suggested immunomodulating mechanisms associated with the tested therapeutic modality. Cell-mediated cytotoxicity represents a key mechanism in the immune response to various pathogens and tumors. Therefore, the selection of monitoring methods for the appropriate assessment of cell-mediated cytotoxicity is thought to be crucial. Assays that can detect both cytotoxic T lymphocytes (CTL) frequency and function, such as the IFN-γ enzyme-linked immunospot assay (ELISPOT) have gained increasing popularity for monitoring clinical trials and in basic research. Results from various clinical trials, including peptide and whole tumor cell vaccination and cytokine treatment, have shown the suitability of the IFN-γ ELISPOT assay for monitoring T cell responses. However, the Granzyme B ELISPOT assay and Perforin ELISPOT assay may represent a more direct analysis of cell-mediated cytotoxicity as compared to the IFN-γ ELISPOT, since Granzyme B and perforin are the key mediators of target cell death via the granule-mediated pathway. In this review we analyze our own data and the data reported by others with regard to the application of various modifications of ELISPOT assays for monitoring CTL activity in clinical vaccine trials

Managing for Change: Achieving Systemic Reform Through the Effective Implementation of Networks for School Improvement

In August 2018, the Bill & Melinda Gates Foundation (“the foundation”) launched its Networks for School Improvement (NSIs) initiative. To further its own continuous learning as well as the learning of its grantees and the educational field, the foundation engaged the Center for Public Research and Leadership (CPRL) to conduct a formative evaluation of the NSIs initiative during its first two years. The research questions that guided this study were: How are network hubs implementing the Network for School Improvement (NSI) strategy? What are the characteristics of effective networks and network hubs? To answer these questions, CPRL used a qualitative research design to deeply explore the work of nine networks representative of the broader pool of grantees. Selection was designed to ensure diversity with respect to the following characteristics: (a) geographic location, (b) number of schools in the network, (c) number of districts in the network, (d) grade band targeted, and (e) problem of practice. The findings presented in this paper emerge from an analysis of data collected from these networks across two years. In total, CPRL conducted over 160 interviews, observed 22 network convenings, and analyzed nearly 1,000 artifacts and documents