Molecular Approaches to Sarcoma Therapy

Soft tissue sarcomas comprise a heterogeneous group of aggressive tumors that have a relatively poor prognosis. Although conventional therapeutic regimens can effectively cytoreduce the overall tumor mass, they fail to consistently achieve a curative outcome. Alternative gene-based approaches that counteract the underlying neoplastic process by eliminating the clonal aberrations that potentiate malignant behavior have been proposed. As compared to the accumulation of gene alterations associated with epithelial carcinomas, sarcomas are frequently characterized by the unique presence of a single chromosomal translocation in each histological subtype. Similar to the Philadelphia chromosome associated with CML, these clonal abnormalities result in the fusion of two independent unrelated genes to generate a unique chimeric protein that displays aberrant activity believed to initiate cellular transformation. Secondary gene mutations may provide an additional growth advantage that further contributes to malignant progression. The recent clinical success of the tyrosine kinase inhibitor, STI571, suggests that therapeutic approaches specifically directed against essential survival factors in sarcoma cells may be effective. This review summarizes published approaches targeting a specific molecular mechanism associated with sarcomagenesis. The strategy and significance of published translational studies in six distinct areas are presented. These include: (1) the disruption of chimeric transcription factor activity; (2) inhibition of growth stimulatory post-translational modifications; (3) restoration of tumor suppressor function; (4) interference with angiogenesis; (5) induction of apoptotic pathways; and (6) introduction of toxic gene products. The potential for improving outcomes in sarcoma patients and the conceptual obstacles to be overcome are discussed

Self Concept As A Mediator Of Effect Of Extracurricular Activities On Academic Engagement in Middle School Students

The following study examined the relationship between participation in extracurricular activities and academic outcomes, such as achievement and behavioral engagement and self-concept, in an at-risk group of middle school students. The researchers hypothesized that if a relationship existed between extracurricular participation and academic outcomes, then self-competence beliefs would mediate this relationship and that these relationships would remain significant after controlling for the previous years’ academic outcomes and self-concept. Consistent with the hypothesis, there was a positive relationship between extracurricular participation and achievement. However, this relationship was no longer significant after controlling for the previous years’ achievement. Inconsistent with the hypothesis, the relationship between extracurricular participation and classroom engagement was not significant. As expected, the positive relationship between extracurricular participation and self-concept was significant and remained significant after controlling for the previous years’ self-concept. The implications of these findings and avenues for further research are discussed

Accommodations experience and retention of students who are deaf or hard-of-hearing in postsecondary education settings

textStudents who are deaf or hard-of-hearing represent a special population of students with unique accommodation needs (Cawthon & Online Research Lab, 2008). The goal of these accommodations, whether utilized during classroom instruction or assessment, is to ensure students have access to academic material and are able to demonstrate their skills on knowledge assessments. These students have historically had less access to higher education and in the last few decades research has examined their low rates of retention in postsecondary institutions (Lang, 2002). Previous research has examined a variety of social and academic factors in relation to retention of deaf or hard-of-hearing students (Albertini, Kelly, & Matchett, 2011). However, this research is often limited to few sites and time windows, rather than examining the longitudinal nature of retention. This dissertation proposed to utilize the deaf or hard-of-hearing sample in the National Longitudinal Transition Study-2 (NLTS2) to examine the extent of the relationship between students’ experiences of accommodations in their postsecondary setting and their retention in that setting. Particular aspects of this experience included student evaluations of their accommodations’ utility and whether they received sufficient accommodations. Analysis included two logistic regression where responses to questions regarding accommodations, controlling for previous school performance, socioeconomic status, and co-occurring disabilities, were used to predict college retention. Analysis also addressed whether the student’s communication modality moderates the relationship between students’ evaluations of accommodations utility and sufficiency and college retention.Educational Psycholog

Progressive Multifocal Leukoencephalopathy in a HIV-Negative Patient with Small Lymphocytic Leukemia following Treatment with Rituximab

We describe a case of progressive multifocal leukoencephalopathy (PML) caused by infection with the human polyomavirus JC virus in a patient with B-cell small lymphocytic leukemia who was treated with rituximab. The first symptoms of PML appeared immediately following the last of five cycles of rituximab, cyclophosphamide and pentostatin. Magnetic resonance imaging revealed changes consistent with PML, although JC virus DNA was not detected by polymerase chain reaction assay of the cerebrospinal fluid. A stereotactic biopsy of the brain showed histological changes consistent with PML, while electron microscopy revealed JC virus particles attached to the nuclei of astrocytes. The patient was treated supportively but died 53 days after the initial onset of symptoms

Thrombotic Thrombocytopenic Purpura Associated with Clopidogrel

BACKGROUND: The antiplatelet drug clopidogrel is a new thienopyridine derivative whose mechanism of action and chemical structure are similar to those of ticlopidine. The estimated incidence of ticlopidine-associated thrombotic thrombocytopenic purpura is 1 per 1600 to 5000 patients treated, whereas no clopidogrel-associated cases were observed among 20,000 closely monitored patients treated in phase 3 clinical trials and cohort studies. Because of the association between ticlopidine use and thrombotic thrombocytopenic purpura and other adverse effects, clopidogrel has largely replaced ticlopidine in clinical practice. More than 3 million patients have received clopidogrel. We report the clinical and laboratory findings in 11 patients in whom thrombotic thrombocytopenic purpura developed during or soon after treatment with clopidogrel. METHODS: The 11 patients were identified by active surveillance by the medical directors of blood banks (3 patients), hematologists (6), and the manufacturer of clopidogrel (2). RESULTS: Ten of the 11 patients received clopidogrel for 14 days or less before the onset of thrombotic thrombocytopenic purpura. Although 10 of the 11 patients had a response to plasma exchange, 2 required 20 or more exchanges before clinical improvement occurred, and 2 had relapses while not receiving clopidogrel. One patient died despite undergoing plasma exchange soon after diagnosis. CONCLUSIONS: Thrombotic thrombocytopenic purpura can occur after the initiation of clopidogrel therapy, often within the first two weeks of treatment. Physicians should be aware of the possibility of this syndrome when initiating clopidogrel treatment

Electromagnetic probing of salt with high frequency radar

Vita.The major thrust of this dissertation is the development, field testing, and theoretical evaluation of a high frequency (HF) radar system for use in probing rock salt where very-high frequency (VHF) radars have failed. The failure of the VHF radars is attributed to high electromagnetic attenuation due to the presence of water in the salt. Due to the conflicting conditions of a decrease in attenuation and a decrease in resolution as the radar frequency decreases, the optimum frequency range for probing wet salt is in the HF region. The Alpha II radar system is a portable, pulsed HF radar system designed to probe in wet salt. It operates at a frequency of 30 MHz with up to 10kW of peak output power, a pulse width of 1 μs, and a repetition frequency of 1 kHz. The travel times of received radar reflections are measured on an oscilloscope and converted to ranges using the radar speed in salt, which is measured in situ by probing through pillars of known thickness. Analog signal processing using a boxcar integrator may be performed to increase the signal-to-noise ratio of the received radar reflections. The Alpha II radar system was successfully field tested within two salt mines: Morton Salt Company's Kleer mine at Grand Saline, Texas, where the salt is dry, and Canadian Salt Company's Ojibway mine near Windsor, Ontario, where the salt is wet.

Electromagnetic probing of salt with high frequency radar

Vita.The major thrust of this dissertation is the development, field testing, and theoretical evaluation of a high frequency (HF) radar system for use in probing rock salt where very-high frequency (VHF) radars have failed. The failure of the VHF radars is attributed to high electromagnetic attenuation due to the presence of water in the salt. Due to the conflicting conditions of a decrease in attenuation and a decrease in resolution as the radar frequency decreases, the optimum frequency range for probing wet salt is in the HF region. The Alpha II radar system is a portable, pulsed HF radar system designed to probe in wet salt. It operates at a frequency of 30 MHz with up to 10kW of peak output power, a pulse width of 1 μs, and a repetition frequency of 1 kHz. The travel times of received radar reflections are measured on an oscilloscope and converted to ranges using the radar speed in salt, which is measured in situ by probing through pillars of known thickness. Analog signal processing using a boxcar integrator may be performed to increase the signal-to-noise ratio of the received radar reflections. The Alpha II radar system was successfully field tested within two salt mines: Morton Salt Company's Kleer mine at Grand Saline, Texas, where the salt is dry, and Canadian Salt Company's Ojibway mine near Windsor, Ontario, where the salt is wet.