The Transformative Power of Social Justice and Leadership: Self, School, and Community

Operating from Burrell and Morgan's (1979) Radical Humanist Paradigm and using Foster's (1986) conception of moral, transformative leadership as a theoretical framework, this dissertation presents three empirical studies that demonstrate the potential for social justice efforts and leadership. Guided by a critical grounded theory approach, the first study represents transformation of self in its analysis of critical consciousness development and praxis in White, privileged individuals. The second study provides an example of school transformation and presents a re-conceptualization of transformational leadership and professional learning communities as a guide for inclusive practices. The final study demonstrates the mutually beneficial components of community/school transformation and responds to critiques of social justice recently presented by the author (2014) and Capper and Young (2014) that social justice efforts in schools have not included transformation of community and the greater society. Furthermore, the article demonstrates the use of motivational theory (Maslow, 1943), originally aimed in educational leadership to increase efficiency, as a guiding principle for social justice and community transformation

Whole Exome Sequencing Identifies Novel Genes for Fetal Hemoglobin Response to Hydroxyurea in Children with Sickle Cell Anemia

<div><p>Hydroxyurea has proven efficacy in children and adults with sickle cell anemia (SCA), but with considerable inter-individual variability in the amount of fetal hemoglobin (HbF) produced. Sibling and twin studies indicate that some of that drug response variation is heritable. To test the hypothesis that genetic modifiers influence pharmacological induction of HbF, we investigated phenotype-genotype associations using whole exome sequencing of children with SCA treated prospectively with hydroxyurea to maximum tolerated dose (MTD). We analyzed 171 unrelated patients enrolled in two prospective clinical trials, all treated with dose escalation to MTD. We examined two MTD drug response phenotypes: HbF (final %HbF minus baseline %HbF), and final %HbF. Analyzing individual genetic variants, we identified multiple low frequency and common variants associated with HbF induction by hydroxyurea. A validation cohort of 130 pediatric sickle cell patients treated to MTD with hydroxyurea was genotyped for 13 non-synonymous variants with the strongest association with HbF response to hydroxyurea in the discovery cohort. A coding variant in <i>Spalt-like transcription factor</i>, or <i>SALL2</i>, was associated with higher final HbF in this second independent replication sample and <i>SALL2</i> represents an outstanding novel candidate gene for further investigation. These findings may help focus future functional studies and provide new insights into the pharmacological HbF upregulation by hydroxyurea in patients with SCA.</p></div

Variants associated with ΔHbF on hydroxyurea.

<p>Variants selected were predicted damaging, with a p-value <0.001 in the discovery cohort, n = 171, composed of patients from HUSTLE and SWiTCH trials.</p><p>Variants associated with ΔHbF on hydroxyurea.</p

Effect of <i>SALL2</i> variant rs61743453 on HbF response to hydroxyurea.

<p>A, Effect of rs61743453 on delta HbF in discovery cohort. B, Effect of rs61743453 on MTD HbF in validation cohort. Variant refers to the Pro840Arg variant; no individuals were homozygous for this change.</p

Variants associated with final HbF on hydroxyurea.

<p>Variants selected were predicted damaging, with a p-value <0.001 in the discovery cohort, n = 171, composed of patients from HUSTLE and SWiTCH trials.</p><p>Variants associated with final HbF on hydroxyurea.</p

Comparison of discovery and validation cohorts.

<p>A, Baseline, or endogenous HbF for the discovery cohort is shown in binned histogram, and distribution of baseline HbF in validation cohort by a line plot. B, Delta HbF for the discovery cohort is shown in binned histogram, and distribution of delta HbF in validation cohort by a line plot. C, Final, or MID HbF for the discovery cohort is shown in binned histogram, and distribution of final, or MID in validation cohort by a line plot.</p

Comparison of discovery and validation cohorts.

<p>WBC: white blood cell count; ANC: absolute neutrophil count; ARC: absolute reticulocyte count; MCV: mean corpuscular volume; HU: hydroxyurea.</p><p>The discovery cohort was composed of 120 patients from HUSTLE and 51 from SWiTCH. The validation cohort was collected from patients treated at TCCH.</p><p>Comparison of discovery and validation cohorts.</p