The Comprehensive Assessment of Leadership for Learning: A Next Generation Formative Evaluation and Feedback System

Recent developments in federal policy have prompted the creation of state evaluation frameworks for principals and teachers that hold educators accountable for effective practices and student outcomes. These changes have created a demand for formative evaluation instruments that reflect current accountability pressures and can be used by schools to focus school improvement and leadership development efforts. The Comprehensive Assessment of Leadership for Learning (CALL) is a next generation, 360-degree on-line assessment and feedback system that reflect best practices in feedback design. Some unique characteristics of CALL include a focus on: leadership distributed throughout the school rather than as carried out by an individual leader; assessment of leadership tasks rather than perceptions of leadership practice; a focus on larger complex systems of middle and high school; and transparency of assessment design. This paper describes research contributing to the design and validation of the CALL survey instrument.

Family Preservation Conference Participants and the Internet: Opinions about On-Line Continuing Education

Development of distance and distributed learning continuing education (CE) opportunities for human services workers requires existence of such CE offerings, participant access to the Internet, knowledge of the Internet's use, and willingness to enroll in such programs. A survey of human services professionals who attended the Family Preservation Annual Conferences in 2000 (N = 230) and 2002 (N - 197) revealed that 92% (n = 206) of 2000 survey participants and 98% (192) of 2002 survey participants have used the Internet, while 76% of 2000 and 56% of 2002 respondents reported no formal training in the use of the Internet and its features. Findings are reported that reveal substantial interest among subjects in the Internet as a medium for continuing education programs for professional development.

ΔNp63 REGULATES A COMPLEX NETWORK OF TARGET GENES IN LIMB AND EPIDERMAL DEVELOPMENT

The skin is composed of two major compartments, the dermis and epidermis. The epidermis forms a barrier to protect the body. The stratified epithelium has self-renewing capacity throughout life, and continuous turnover is mediated by stem cells in the basal layer. p63 is structurally and functionally related to p53. In spite of their structural similarities, p63 is critical for the development and maintenance of stratified epithelial tissues, unlike p53. p63 is highly expressed in the epidermis and previously has been shown to play a critical role in the development and maintenance of the epidermis. The study of p63 has been complicated due to the existence of multiple isoforms: those with a transactivation domain (TAp63) and those lacking this domain (ΔNp63). Mice lacking p63 cannot form skin, have craniofacial and skeletal defects and die within hours after birth. These defects are due to the ability of p63 to regulate multiple processes in skin development including epithelial stem cell proliferation, differentiation, and adherence programs. To determine the roles of these isoforms in skin development and maintenance, isoform specific p63 conditional knock out mice were generated by our lab. TAp63-/- mice age prematurely, develop blisters, and display wound-healing defects that result from hyperproliferation of dermal stem cells. That results in premature depletion of these cells, which are necessary for wound repair, that indicates TAp63 plays a role in dermal/epidermal maintenance. To study the role of ΔNp63, I generated a ΔNp63-/- mouse and analyzed the skin by performing immunofluorescence for markers of epithelial differentiation. The ΔNp63-/- mice developed a thin, disorganized epithelium but differentiation markers were expressed. Interestingly, the epidermis from ΔNp63-/- mice co-expressed K14 and K10 in the same cell suggesting defects in epidermal differentiation and stratification. This phenotype is reminiscent of the DGCR8fl/fl;K14Cre and Dicerfl/fl;K14Cre mice skin. Importantly, DGCR8-/- embryonic stem cells (ESCs) display a hyperproliferation defect by failure to silence pluripotency genes. Furthermore, I have observed that epidermal cells lacking ΔNp63 display a phenotype reminiscent of embryonic stem cells instead of keratinocytes. Thus, I hypothesize that genes involved in maintaining pluripotency, like Oct4, may be upregulated in the absence of ΔNp63. To test this, q-RT PCR was performed for Oct4 mRNA with wild type and ΔNp63-/- 18.5dpc embryo skin. I found that the level of Oct4 was dramatically increased in the absence of ΔNp63-/-. Based on these results, I hypothesized that ΔNp63 induces differentiation by silencing pluripotency regulators, Oct4, Sox2 and Nanog directly through the regulation of DGCR8. I found that DGCR8 restoration resulted in repression of Oct4, Sox2 and Nanog in ΔNp63-/- epidermal cells and rescue differentiation defects. Loss of ΔNp63 resulted in pluripotency that caused defect in proper differentiation and stem cell like phenotype. This led me to culture the ΔNp63-/- epidermal cells in neuronal cell culture media in order to address whether restoration of DGCR8 can transform epidermal cells to neuronal cells. I found that DGCR8 restoration resulted in a change in cell fate. I also found that miR470 and miR145 play a role in the induction of pluripotency by repressing Oct4, Sox2 and Nanog. This indicates that ΔNp63 induces terminal differentiation through the regulation of DGCR8.

Molecular mechanisms underlying a cellular analog of operant reward learning.

Operant conditioning is a ubiquitous but mechanistically poorly understood form of associative learning in which an animal learns the consequences of its behavior. Using a single-cell analog of operant conditioning in neuron B51 of Aplysia, we examined second-messenger pathways engaged by activity and reward and how they may provide a biochemical association underlying operant learning. Conditioning was blocked by Rp-cAMP, a peptide inhibitor of PKA, a PKC inhibitor, and by expressing a dominant-negative isoform of Ca2+-dependent PKC (apl-I). Thus, both PKA and PKC were necessary for operant conditioning. Injection of cAMP into B51 mimicked the effects of operant conditioning. Activation of PKC also mimicked conditioning but was dependent on both cAMP and PKA, suggesting that PKC acted at some point upstream of PKA activation. Our results demonstrate how these molecules can interact to mediate operant conditioning in an individual neuron important for the expression of the conditioned behavior.

Role of germ line p53 mutations in aneuploidy and immortalization of dermal fibroblasts from Li-Fraumeni cancer patients

Pedigree analysis of certain families with a high incidence of tumors suggests a genetic predisposition to cancer. Li and Fraumeni described a familial cancer syndrome that is characterized by multiple primary tumors, early age of onset, and marked variation in tumor type. Williams and Strong (1) demonstrated that at least 7% of childhood soft tissue sarcoma patients had family histories that is readily explained by a highly penetrant autosomal dominant gene. To characterize the mechanism for genetic predisposition to many tumor types in these families, we have studied genetic alterations in fibroblasts, a target tissue from patients with the Li-Fraumeni Syndrome (LFS).^ We have observed spontaneous changes in initially normal dermal fibroblasts from LFS patients as they are cultured in vitro. The cells acquire an altered morphology, chromosomal anomalies, and anchorage-independent growth. This aberrant behavior of fibroblasts from LFS patients had never been observed in fibroblasts from normal donors. In addition to these phenotypic alterations, patient fibroblasts spontaneously immortalize by 50 population doublings (pd) in culture; unlike controls that remain normal and senesce by 30-35 (2). At 50 pd, immortal fibroblasts from two patients were found to be susceptible to tumorigenic transformation by an activated T24 H-ras oncogene (3). Approximately 80% of the oncogene expressing transfectants were capable of forming tumors in nude mice within 2-3 weeks. p53 has been previously associated with immortalization of cells in culture and cooperation with ras in transfection assays. Therefore, patients' fibroblast and lymphocyte derived DNA was tested for point mutations in p53. It was shown that LFS patients inherited certain point mutations in one of the two p53 alleles (4). Further studies on the above LFS immortal fibroblasts have demonstrated loss of the remaining p53 allele concomitant with escape from senescence. While the loss of the second allele correlates with immortalization it is not sufficient to transformation by an activated H-ras or N-ras oncogene. These immortal fibroblasts are resistant to tumorigenic transformation by v-abl, v-src, c-neu or v-mos oncogene; implying that additional steps are required in the tumorigenic progression of LFS patients' fibroblasts.^ References. (1) Williams et al., J. Natl. Cancer Inst. 79:1213, 1987. (2) Bischoff et al., Cancer Res. 50:7979, 1990. (3) Bischoff et al., Oncogene 6:183, 1991. (4) Malkin et al., Science 250:1233, 1990. ^

Application of cell line based genomic predictors to predict response to targeted therapies in breast cancer

Cancer cell lines can be treated with a drug and the molecular comparison of responders and non-responders may yield potential predictors that could be tested in the clinic. It is a bioinformatics challenge to apply the cell line-derived multivariable response predictors to patients who respond to therapy. Using the gene expression data from 23 breast cancer cell lines, I developed three predictors of dasatinib sensitivity by selecting differentially expressed genes and applying different classification algorithms. The performance of these predictors on independent cell lines with known dasatinib response was tested. The predictor based on weighted voting method has the best overall performance. It correctly predicted dasatinib sensitivity in 11 out of 12 (92%) breast and 17 out of 23 (74%) lung cancer cell lines. These predictors were then applied to the gene expression data from 133 breast cancer patients in an attempt to predict how the patients might respond to dasatinib therapy. Two predictors identified 13 patients in common to be dasatinib sensitive. Sixty two percent of these cases are triple negative (ER-negative, HER2-negative and PR-negative) and 76% are double negative. The result is consistent with the findings from other studies, which identified a target population for dasatinib treatment to be triple negative or basal breast cancer subtype. In conclusion, we think that the cell line-derived dasatinib classifiers can be applied to the human patients. ^

The cost effective management of Central Line-Associated Bloodstream Infections (CLABSIs) comparing the central line bundle to antimicrobialcoated central venous catheters: A systematic review

Central Line-Associated Bloodstream Infections (CLABSIs) are one of the most costly and preventable cases of morbidity and mortality among intensive care units (ICUs) in health care today. In 2008, the Centers for Medicare and Medicaid Services Medicare Program, under the Deficit Reduction Act, announced it will no longer reimburse hospitals for such adverse events among those related to CLABSIs. This reveals the financial burden shift onto the hospital rather than the health care payer who can now withhold reimbursements. With this weighing more heavily on hospital management, decision makers will need to find a way to completely prevent cases of CLABSI or simply pay for the financial consequences. ^ To reduce the risk of CLABSIs, several clinical, preventive interventions have been studied and even instituted including the Central Line (CL) Bundle and Antimicrobial Coated Central Venous Catheters (AM-CVCs). I carried out a formal systematic review on the topic to compare the cost-effectiveness of the Central Line (CL) Bundle to the commercially available antimicrobial coated central venous catheters (AM-CVCs) in preventing CLABSIs among critically and chronically ill patients in the U.S. Evidence was assessed for inclusion against predefined criteria. I, myself, conducted the data extraction. Ten studies were included in the review. Efficacy in reducing the mean incidence rate of CLABSI by the CL Bundle and AM-CVC interventions were compared with one another including costs. ^ The AM-CVC impregnated with antibiotics, rifampin-minocycline (AI-RM) is more clinically effective than the CL Bundle in reducing the mean rate of CLABSI per 1,000 catheter days. The lowest mean incidence rate of CLABSI per 1,000 catheter days among the AM-CVC studies was as low as zero in favor of the AI-RM. Moreover, the review revealed that the AI-RM appears to be more cost-effective than the CL Bundle. Results showed the adjusted incremental cost of the CL Bundle per ICU patient requiring a CVC to be approximately $196 while the AI-RM at only an additional cost of $48 per ICU patient requiring a CVC. ^ Limited data regarding the cost of the CL Bundle made it difficult to make a true comparison to the direct cost of the AM-CVCs. However, using the result I did have from this review, I concluded that the AM-CVCs do appear to be more cost-effective in decreasing the mean rate of CLABSI while also minimizing incremental costs per CVC than the CL Bundle. This review calls for further research addressing the cost of the CL Bundle and compliance and more effective study designs such as randomized control trials comparing the efficacy and cost of the CL Bundle to the AM-CVCs. Barriers that may face health care managers when implementing the CL Bundle or AM-CVCs include additional costs associated with the intervention, educational training and ongoing reinforcement as well as creating a new culture of understanding.^

Commentary on "Expanded Learning Time in Schools"

As co-founder of KIPP, I know from experience and research that more time in school works. A well-designed extended-time program can help underserved students catch up academically, and prepare them for the rigors of higher education. Implementing extended time more widely poses challenges, but there are also creative solutions to these challenges.