SRB Environment Evaluation and Analysis. Volume 3: ASRB Plume Induced Environments

Contract NAS8-37891 was expanded in late 1989 to initiate analysis of Shuttle plume induced environments as a result of the substitution of the Advanced Solid Rocket Booster (ASRB) for the Redesigned Solid Rocket Booster (RSRB). To support this analysis, REMTECH became involved in subscale and full-scale solid rocket motor test programs which further expanded the scope of work. Later contract modifications included additional tasks to produce initial design cycle environments and to specify development flight instrumentation. Volume 3 of the final report describes these analyses and contains a summary of reports resulting from various studies

Surveys of Stylisma Pickeringii var. Pattersonii (Convolvulaceae), its Associated Plant Species, and its Insect Visitors

Stylisma pickeringii var. pattersonii (Convolvulaceae) is endangered in Illinois and Iowa, and occurs in scattered populations in other states. During 1999 and 2000, two insect species previously unreported from Illinois were observed visiting its flowers. This study was undertaken to survey additional insect visitors, as well as to characterize the plant community where S. pickeringii occurs. The objectives were to survey: 1) floral traits (anthesis and flower density) of S. pickeringii, 2) associated plant species, and 3) insect visitor characteristics. Floral traits were determined and associated plant species surveyed in Mason County (degraded hay field on private property) and Henderson County (dry sand prairie at the Big River State Forest), Illinois. Insects visiting flowers were collected at 10:00 a.m., 12:30 p.m., and 3:00 p.m. during June, July, and August in 2001 and 2002. Individual flowers lasted one day and remained open for 6–8 hours. Peak flowering occurred from early to the middle of July when S. pickeringii was the dominant species in flower. Henderson County contained a greater diversity of native plant species with less bare ground and fewer non-native species than the Mason County site. Fortyseven insect species were observed visiting S. pickeringii flowers. Most frequent visitors were Apis mellifera (Hymenoptera: Apidae), Bombylius fraudulentus (Diptera: Bombyliidae), and Heterostylum croceum (Diptera: Bombliidae). The diversity of visiting insects was higher earlier than later in the day, in July and August than June, and in Henderson than Mason County

Reevaluating the imaging definition of tumor progression: perfusion MRI quantifies recurrent glioblastoma tumor fraction, pseudoprogression, and radiation necrosis to predict survival

INTRODUCTION: Contrast-enhanced MRI (CE-MRI) represents the current mainstay for monitoring treatment response in glioblastoma multiforme (GBM), based on the premise that enlarging lesions reflect increasing tumor burden, treatment failure, and poor prognosis. Unfortunately, irradiating such tumors can induce changes in CE-MRI that mimic tumor recurrence, so called post treatment radiation effect (PTRE), and in fact, both PTRE and tumor re-growth can occur together. Because PTRE represents treatment success, the relative histologic fraction of tumor growth versus PTRE affects survival. Studies suggest that Perfusion MRI (pMRI)–based measures of relative cerebral blood volume (rCBV) can noninvasively estimate histologic tumor fraction to predict clinical outcome. There are several proposed pMRI-based analytic methods, although none have been correlated with overall survival (OS). This study compares how well histologic tumor fraction and OS correlate with several pMRI-based metrics. METHODS: We recruited previously treated patients with GBM undergoing surgical re-resection for suspected tumor recurrence and calculated preoperative pMRI-based metrics within CE-MRI enhancing lesions: rCBV mean, mode, maximum, width, and a new thresholding metric called pMRI–fractional tumor burden (pMRI-FTB). We correlated all pMRI-based metrics with histologic tumor fraction and OS. RESULTS: Among 25 recurrent patients with GBM, histologic tumor fraction correlated most strongly with pMRI-FTB (r = 0.82; P < .0001), which was the only imaging metric that correlated with OS (P<.02). CONCLUSION: The pMRI-FTB metric reliably estimates histologic tumor fraction (i.e., tumor burden) and correlates with OS in the context of recurrent GBM. This technique may offer a promising biomarker of tumor progression and clinical outcome for future clinical trials

Evidence for D1 Dopamine Receptor Activation by a Paracrine Signal of Dopamine in Tick Salivary Glands

Ticks that feed on vertebrate hosts use their salivary secretion, which contains various bioactive components, to manipulate the host's responses. The mechanisms controlling the tick salivary gland in this dynamic process are not well understood. We identified the tick D1 receptor activated by dopamine, a potent inducer of the salivary secretion of ticks. Temporal and spatial expression patterns examined by immunohistochemistry and reverse transcription polymerase chain reaction suggest that the dopamine produced in the basal cells of salivary gland acini is secreted into the lumen and activates the D1 receptors on the luminal surface of the cells lining the acini. Therefore, we propose a paracrine function of dopamine that is mediated by the D1 receptor in the salivary gland at an early phase of feeding. The molecular and pharmacological characterization of the D1 receptor in this study provides the foundation for understanding the functions of dopamine in the blood-feeding of ticks

CIP2A expression predicts recurrences of tamoxifen-treated breast cancer

CIP2A is emerging as an oncoprotein overexpressed commonly across many tumours and generally correlated with higher tumour grade and therapeutic resistance. CIP2A drives an oncogenic potential through inhibiting protein phosphatase 2A, stabilizing MYC, and promoting epithelial-to-mesenchymal transition, although further biological mechanisms for CIP2A are yet to be defined. CIP2A protein expression was studied by immunohistochemistry in oestrogen receptor–positive primary breast cancers (n = 250) obtained from the Leeds Tissue Bank. In total, 51 cases presented with a relapse or metastasis during adjuvant treatment with tamoxifen and were regarded as tamoxifen resistant. CIP2A expression was scored separately for cytoplasmic, nuclear, or membranous staining, and scores were tested for statistically significant relationships with clinicopathological features. Membranous CIP2A was preferentially expressed in cases who experienced a recurrence during tamoxifen treatment thus predicting a worse overall survival (log rank = 8.357, p = 0.004) and disease-free survival (log rank = 21.766, p < 0.001). Cox multivariate analysis indicates that it is an independent prognostic indicator for overall survival (hazard ratio = 4.310, p = 0.013) and disease-free survival (hazard ratio = 5.449, p = 0.002). In this study, we propose the assessment of membranous CIP2A expression as a potential novel prognostic and predictive indicator for tamoxifen resistance and recurrence within oestrogen receptor–positive breast cancer

Evaluating the discriminatory power of EQ-5D, HUI2 and HUI3 in a US general population survey using Shannon’s indices

OBJECTIVES: To compare quantitatively the discriminatory power of the EQ-5D, HUI2 and HUI3 in terms of absolute and relative informativity, using Shannon's indices. METHODS: EQ-5D and HUI2/3 data completed by a sample of the general adult US population (N = 3,691) were used. Five dimensions allowed head-to-head comparison of informativity: Mobility/Ambulation; Anxiety/Depression/Emotion; Pain/Discomfort (EQ-5D; HUI2; HUI3); Self-Care (EQ-5D; HUI2); and Cognition (HUI2; HUI3). Shannon's index and Shannon's Evenness index were used to assess absolute and relative informativity, both by dimension and by instrument as a whole. RESULTS: Absolute informativity was highest for HUI3, with the largest differences in Pain/Discomfort and Cognition. Relative informativity was highest for EQ-5D, with the largest differences in Mobility/Ambulation and Anxiety/Depression/Emotion. Absolute informativity by instrument was consistently highest for HUI3 and lowest for EQ-5D, and relative informativity was highest for EQ-5D and lowest for HUI3. DISCUSSION: Performance in terms of absolute and relative informativity of the common dimensions of the three instruments varies over dimensions. Several dimensions are suboptimal: Pain/Discomfort (EQ-5D) seems too crude with only 3 levels, and the level descriptions of Ambulation (HUI3) and Self-Care (HUI2) could be improved. In absence of a formal measure, Shannon's indices provide useful measures for assessing discriminatory power of utility instrument

Multi-site investigation of strategies for the implementation of CYP2C19 genotype-guided antiplatelet therapy

CYP2C19 genotype-guided antiplatelet therapy following percutaneous coronary intervention is increasingly implemented in clinical practice. However, challenges such as selecting a testing platform, communicating test results, building clinical decision support processes, providing patient and provider education, and integrating methods to support the translation of emerging evidence to clinical practice are barriers to broad adoption. In this report, we compare and contrast implementation strategies of 12 early adopters, describing solutions to common problems and initial performance metrics for each program. Key differences between programs included the test result turnaround time and timing of therapy changes which are both related to CYP2C19 testing model and platform used. Sites reported the need for new informatics infrastructure, expert clinicians such as pharmacists to interpret results, physician champions, and ongoing education. Consensus lessons learned are presented to provide a path forward for those seeking to implement similar clinical pharmacogenomics programs within their institutions. This article is protected by copyright

Histopathological grading of pediatric ependymoma: reproducibility and clinical relevance in European trial cohorts

<p>Abstract</p> <p>Background</p> <p>Histopathological grading of ependymoma has been controversial with respect to its reproducibility and clinical significance. In a 3-phase study, we reviewed the pathology of 229 intracranial ependymomas from European trial cohorts of infants (2 trials - SFOP/CNS9204) and older children (2 trials - AIEOP/CNS9904) to assess both diagnostic concordance among five neuropathologists and the prognostic utility of histopathological variables, particularly tumor grading.</p> <p>Results</p> <p>In phase 1, using WHO criteria and without first discussing any issue related to grading ependymomas, pathologists assessed and independently graded ependymomas from 3 of 4 trial cohorts. Diagnosis of grade II ependymoma was less frequent than grade III, a difference that increased when one cohort (CNS9204) was reassessed in phase 2, during which the pathologists discussed ependymoma grading, jointly reviewed all CNS9204 tumors, and defined a novel grading system based on the WHO classification. In phase 3, repeat independent review of two cohorts (SFOP/CNS9904) using the novel system was associated with a substantial increase in concordance on grading. Extent of tumor resection was significantly associated with progression-free survival (PFS) in SFOP and AIEOP, but not in CNS9204 and CNS9904. Strength of consensus on grade was significantly associated with PFS in only one trial cohort (AIEOP). Consensus on the scoring of individual histopathological features (necrosis, angiogenesis, cell density, and mitotic activity) correlated with PFS in AIEOP, but in no other trial.</p> <p>Conclusions</p> <p>We conclude that concordance on grading ependymomas can be improved by using a more prescribed scheme based on the WHO classification. Unfortunately, this appears to have utility in limited clinical settings.</p