Modeling Human Cancer Therapy Response in Patient Derived Xenografts

Patient‐derived xenografts (PDXs) generated by implanting human tumor tissue into a transplant compliant mouse host have been of increasingly importance to preclinical development and have been demonstrated to have advantages compared to cancer cell lines and cell‐line xenografts (CLX) for modeling therapeutic responses in cancer. Nevertheless, many open questions remain regarding the relationship between study design factors and classification of treatment response and the molecular fidelity of tumors passaged in PDXs relative to the original patient tumor(s). The research described in this dissertation addresses both of these significant issues related to the use of PDXs as a tool for modeling human cancer therapy response. This work investigated how study design factors (enrollment criteria, group size, study duration) and data analysis method influenced treatment responses in PDXs. Each of the methods evaluated consistently classified responsiveness which suggests it is feasible to ii combine response data across studies that apply different methods assuming consistent response value thresholds have been used. The results demonstrated that a cohort size of three is sufficient for identifying the four highly responsive and nine highly non‐responsive cisplatin treated tumors, suggesting that the use of a low cohort size to screen for chemotherapies that have a high degree of activity or models that are highly responsive is possible. Mutational and expression profiles of engrafted tumors were compared with the original patient tumors and demonstrated that the molecular fidelity of PT and passaged tumors is high at a global level; the majority of variants with known clinical significance are preserved between PT and PDX tumors. However, individual markers are not invariably concordant and in some cases the molecular discrepancies observed between PDX and PT occurred in variants that are clinically relevant to either disease prognosis or to selection of therapy. Confirming the mutation status of donor tumors used to establish testing cohorts should be routine practice when PDXs are used as models for modeling treatment responses of individual patients

Gender Life Course Transitions from the Nuclear Family in England and Wales 1981-2001

In recent years there has been much political debate in the popular media about the fate of the nuclear family in the UK. Very little work has been done, using population data, to actually demonstrate the decline, or indeed continuance of this type of household formation. In this paper we use Office for National Statistics (ONS) longitudinal census data, from England and Wales, to explore the formation, dissolution and continuance of the nuclear family household over a twenty year period (1981- 2001). Our findings indicate a continuing importance of this household arrangement, however routes into and trajectories from nuclear family households take different forms for men and women across the life course.Nuclear Family; Households; Gender; Longitudinal Analysis

Gibberellin metabolism in seeds and seedlings of the runner bean, Phaseolus coccineus L

An investigation was made of GA metabolism in Phaseolus coccineus L., cv. Prizewinner using an in vitro preparation from immature seeds. GA12-aldehyde underwent non-13-hydroxylated conversion to GA4 via GA12, GA15, GA24, GA36 and GA37 and was metabolised to GA1 via a 13-hydroxylated pathway encompassing GA19, GA20, GA44 and GA53. GAa was not 13-hydroxylated to produce GA1. Key incubations were performed using an in vitro preparation from immature seeds of a dwarf variety, Hammonds Dwarf Scarlet, but no metabolic differences were observed between dwarf and tall cultivars. GA1 was not 2P-hydroxylated to form GA8. The nature of the 3p-hydroxylating enzyme from immature seeds was investigated by fast protein liquid chromatography (FPLC) separation of the crude cell-free preparations from Prizewinner and Hammonds Dwarf Scarlet Following assay of the FPLC fractions, sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) of zones which converted [3H]GA20 to [3H]GA1 was carried out. Preliminary analysis revealed similarities between the polypeptides of both cultivars. In order to investigate GA metabolism in seedlings, [3H]-labelled GAs were applied to cvs. Prizewinner and Hammonds Dwarf Scarlet. In contrast to metabolism by the cell-free preparations from immature seeds, [3H]GA4 as well as [3H]GA20 was converted to [3H]GA1 which was further converted to [3H]GA8, in seedlings of each variety. It was concluded that the dwarf growth habit exhibited by seedlings of Hammonds Dwarf Scarlet was not simply a consequence of an inability to synthesise GA1. A study of the endogenous GA20 content of the dwarf and tall seedlings showed mean values of 1.14 ng g-1 fresh weight and 0.95 ng g-1 fresh weight, respectively

Relationship satisfaction as a function of the discrepancy between experienced and desired levels of intimacy

The present study investigated the effect of discrepancies between experienced versus desired levels ·of intimacy on relationship satisfaction using data from 135 undergraduate students. Subjects completed the Personal Assessment of Intimacy in Relationships (PAIR), the Dyaqic Relationship Questionnaire (DRQ), the Dyadic Adjustment Scale (DAS), and a Background Questionnaire (BQ).Correlation and multiple regression analyses indicated that discrepancies between Desired and Experienced Intimacy, as measured by the PAIR and DRQ, was highly predictive of relationship satisfaction, as measured by the DAS. However, Experienced Intimacy was a better predictor of relationship satisfaction. Both males and females ranked Emotional Intimacy as most important to relationship satisfaction and it was also the strongest predictor of relationship satisfaction. The DRQ was found to be an efficacious pictorial assessment of intimacy.Joan I MalcolmNot ListedNot ListedDoctor of PsychologyDepartment of PsychologyCunningham Memorial library, Terre Haute,Indiana State UniversityILL-ETD-036DoctoralTitle from document title page. Document formatted into pages: contains 57 p.: ill. Includes abstract and appendix

Adapting a Curriculum Unit to Facilitate Interaction Between Technology, Mathematics and Science in the Elementary Classroom: Identifying Relevant Criteria

Calls for the integration of subjects continue to emanate from a wide range of professional bodies, including governments and subject associations. Yet as some authors suggest, blurring the boundaries between subjects may be one of the most daunting tasks educators face. The authors have recently begun a research study that will investigate the extent to which (a) relevant mathematics and science can be made explicit in a technology curriculum unit, (b) pupils utilise this mathematics and science learning, and (c) pupils' ability to design is enhanced by making the mathematics and science explicit and useful. This paper reports the results of Phase 1 of the study: an examination of research literature in order to identify criteria to inform the re-writing of an existing technology curriculum (to be used as a research instrument) that previously did not make explicit embedded mathematics and science concepts. Our reading of the literature has identified two essential criteria that must be met during the re-writing: (a) protecting the integrity of the subjects and (b) identifying the nature and purpose of the intended learning

Factors that influence response classifications in chemotherapy treated patient-derived xenografts (PDX).

In this study, we investigated the impact of initial tumor volume, rate of tumor growth, cohort size, study duration, and data analysis method on chemotherapy treatment response classifications in patient-derived xenografts (PDXs). The analyses were conducted on cisplatin treatment response data for 70 PDX models representing ten cancer types with up to 28-day study duration and cohort sizes of 3-10 tumor-bearing mice. The results demonstrated that a 21-day dosing study using a cohort size of eight was necessary to reliably detect responsive models (i.e., tumor volume ratio of treated animals to control between 0.1 and 0.42)-independent of analysis method. A cohort of three tumor-bearing animals led to a reliable classification of models that were both highly responsive and highly nonresponsive to cisplatin (i.e., tumor volume ratio of treated animals to control animals less than 0.10). In our set of PDXs, we found that tumor growth rate in the control group impacted treatment response classification more than initial tumor volume. We repeated the study design factors using docetaxel treated PDXs with consistent results. Our results highlight the importance of defining endpoints for PDX dosing studies when deciding the size of cohorts to use in dosing studies and illustrate that response classifications for a study do not differ significantly across the commonly used analysis methods that are based on tumor volume changes in treatment versus control groups

Measuring higher education quality

The panelists indicated that considerable progress is being made by such organizations as ACT and NCHEMS in identifying the domains of quality to be measured and particularly in devising unidimensional indicators of student progress. Few were able to cite comparable advancements in the development of multivariate techniques to assess the relation of student growth to other variables. Notable progress in achieving consensus on appropriate standards for measuring quality institutions or curricular programs within comparable institutions remains as a future task.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43587/1/11162_2004_Article_BF00991828.pd

Marine-derived n-3 fatty acids therapy for stroke

We thank the Cochrane Stroke Group, and in particular Hazel Fraser (Managing Editor) and Joshua Cheyne (Trials Search Coordinator and Information Specialist), for their support in the development of this protocol. CG Alvarez Campano is funded by the Mexican Council for Science and Technology (CONACyT) and the Institute of Innovation and Technology Transfer (I²T²) (grant number 457349).Peer reviewedPublisher PD

Prediction of Revised Token Test Overall, Subtest, and Linguistic Unit Scores by Two Shortened Versions

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